Correlating 13C Isotope in Oligomeric Proanthocyanidins with their Anticancer Properties

Cancer is abnormal cell reproduction exhibiting unusual metabolic processes. Cancer occurs as cells alter various normal catabolic and anabolic metabolisms. Warburg Effect involves accelerated glycolysis and suppressed Kreb cycle (catabolism). Glycolysis is catabolic process of enzymatic conversion of glucose to pyruvate. The cellular transformations to cancer lead to accelerated glycolysis. Kreb cycle is catabolic enzymatic conversion of pyruvate to carbon dioxide. The cellular transformations to cancer lead to suppression of Kreb cycle. The anabolism of genetic code is also altered during cancer formation as DNA replications and RNA transcriptions are altered (chaotically and anabolically). Such anabolic chaos with also altered consequent protein translations leads to cancer cell genesis and multiplying genetically altered cells rapidly. In this theory, the anabolic alterations of genes cause altered protein translations for producing proteins of glycolysis that accelerate glycolysis while producing proteins, associated with Kreb cycle that suppress the Kreb cycle. A big mystery of cancer is the nature and mechanism of the DNA mutation, RNA mutation and altered protein translations. In this work, the prior theory ^{1, 2, 3} that nonprimordial isotopes drive, DNA, RNA and protein alterations for cancer is substantiated and the use of nonprimordials to alter cancer metabolism for new treatments of cancer is further stressed.

In this work, the theory ^{1, 2, 3} of stable isotopic replacements and substitutions of primordial, stable ¹H, ¹²C, ¹⁴N, ¹⁶O, and ³²S by nonprimordial, stable ²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S is further developed. This work focuses more on DNA, nucleotides and telomeres. Prior papers focused on glycolysis and Kreb cycle. In normal cells, the ends of DNA have unbounded, telomeric regions, which are shortened to terminate replications of genes, but in cancer the telomeres do not shorten and induce apoptosis. But in cancer, the telomeres mutate and involve telomerase with acceleration of replications ⁴. Telomerase is a protein that is associated with elongations of telomeres. It is unknown why shorten telomeres in cancer cells continue to replicate by telomerases and accelerate replications and transcriptions of DNA and RNA. In this work, the epigenetic stable-isotopic alterations by nonprimordial isotopes (²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S) of DNA, RNA and consequent proteins during normal cells to cancer cells transformations are proposed for fundamental chemistry of cancer’s origins and habitats ^{1, 2, 3} and possibly explain why the shorten telomere in cancer continue to replicate rather than terminate cell life as the shorten telomeres in normal cells.

This theory ^{1, 2, 3} determines that isotopic replacements in normal cells with epigenetic modifications prevent the shortening of the telomeres for causing apoptosis for causing cancer. The nonprimordial isotopes cause such alternations by interfering with signaling to apoptosis by the nonprimordials binding of the telomeres for causing consequent continued replication of the DNA with more and more replications; such that the DNA becomes too bond specifically enriched in nonprimordial isotopes (²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S) of different nuclear magnetic moments (NMMs) ^{1, 2, 3} for normal cellular functioning. But with aging of the host (unusual diet and/or external magnetism), this theory ^{1, 2, 3} proposes more and more biomolecules bond-specifically enrich in the nonprimordial isotopes (²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S) in specific bonds relative to the primordial isotopes (¹H, ¹²C, ¹⁴N, ¹⁶O, ²⁴Mg and ³²S) for greater probability of simultaneous, multiple nonprimordial clumpings in specific bonds in both proteins and nucleic acids. On such basis, the simultaneous nonprimordials in the proteins and the DNA and RNA prevent the normal telomeric (and other gene expressions) induced cell apoptosis by primordial isotopic interactions with the proteins. The nonprimordial isotopes interacting between the telomere and telomerase prevent apoptosis for causing continued cancerous DNA, RNA, and protein reproductions and malfunctions of the normal cells to transform them to carcinomic cells by the prior theory ^{1, 2, 3}. The prior theory ^{1, 2, 3} proposes that the clumpings of nonprimordial isotopes in specific bonds in the telomeres change the binding of the base pairs in the genes, so that the shorter telomeres (and indeed for other genes and their expressions) do not express apoptosis as the telomeres are bound more tightly by the nonprimordial isotopes. The telomeric genes are bound more strongly to binding proteins for telomerase expression. So that the stronger bound nonprimordial, isotopic, shorter telomeres continue to allow the DNA to replicate and the resulting nonprimordial DNA to replicate further to transcribe nonprimordial RNA and the resulting nonprimordial RNA continues to produce nonprimordial proteins. In the DNA and RNA, the accumulations of nonprimordials by ²D, ¹³C¹H₃, ¹⁵N¹H₂ and ¹⁷O¹H (and ¹³C²D¹H₂, ¹⁵N²D₂¹H, ¹⁷O²D) functional replacements on nucleotides of guanosine (G), adenosine (A), cytidine (C), uridine (U) and thymidine (T) rather than primordial ¹H, ¹²C¹H₃, ¹⁴N¹H₂, ¹⁶O¹H replacements cause altered, stronger bonding of the AT and GC in nonprimordial DNA and stronger, altered bonding of AU and GC in nonprimordial RNA. By the author’s model ^{1, 2, 3}, the nonprimordial isotopes in the ²D, ¹³C¹H₃, ¹⁵N¹H₂ and ¹⁷O¹H (and ¹³C²D¹H₂, ¹⁵N²D₂¹H, ¹⁷O²D) on guanosine, adenosine, cytidine, uridine and thymidine cause magnetic bondings in addition to the hydrogen bondings to reduce and hinder the separations of the DNA base pairs for causing normal cells to transform to cancer cells. But by the prior theory ^{1, 2, 3}, such can cause greater nonprimordial uptakes by the cancer DNA; so new treatments are possible as here with proanthocyanidins as the overall nonprimordial bond-specific enriched cancer DNA becomes less separable with killing of the cancer cells by over isotopically enriching the nucleic acids and proteins in the cancer.

The altered enzymatics of proteins and nucleic acids as by this prior theory ^{1, 2, 3} of cancer are based upon the different nuclear magnetic moments (NMMs) and masses of nonprimordial isotopes (²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S) relative to primordial isotopes (¹H, ¹²C, ¹⁴N, ¹⁶O, ²⁴Mg and ³²S) as well as their tiny relative mass differences. Hydrogen has 2 important stable isotopes with different NMMs, spins, masses and relative abundances: ¹H {99.988%, 1 ½ (I) spin, 2.79 (µ/µ_N) NMM} and ²D {0.0115%, 0 (I) spin, (µ/µ_N) ) NMM}. Carbon has 2 important stable isotopes with different NMMs, relative abundances, masses and spins: ¹²C {98.9%, O (I) spin, 0 (µ/µ_N) NMM} and ¹³C {1.1%, ½ (I) spin, 0.70 (µ/µ_N) NMM}. Nitrogen has 2 important stable isotopes with different NMMs, relative abundances, masses and spins: ¹⁴N {99.6%, 1 (I) spin, 0.40 (µ/µ_N) NMM} and ¹⁵N {0.4%, ½ (I) spin, -0.28 (µ/µ_N) NMM}. Oxygen has 3 important isotopes with different NMMs, spins, masses and relative abundances: ¹⁶O {99.8%, 0 (I) spin, 0 (µ/µ_N) NMM}, ¹⁷O {0.03%, 5/2 (I) spin, -1.89 (µ/µ_N) NMM, ¹⁸O {0.205%, 0 (I) spin, 0 (µ/µ_N) NMM}. Magnesium has 3 important isotopes with different NMMs, spins, masses and relative abundances: ²⁴Mg {79.0%, 0 (I) spin, 0 (µ/µ_N) NMM} ,²⁵Mg {10.0%, 3/2 (I) spin, -0.86 (µ/µ_N) NMM}, ²⁶Mg {11.0%, 0 (I) spin, 0 (µ/µ_N) NMM}. Phosphorus has 1 important isotope: ³¹P {100%, ½ (I) spin, 1.13 (µ/µ_N) NMM}. Sulfur has 3 important isotopes with different NMMs, spins, masses and relative abundances: ³²S {94.9%, 0(I) spin, 0 (µ/µ_N) NMM}, ³³S {0.8%, 3/2 (I) spin, 0.64 (µ/µ_N) NMM}, ³⁴S {4.3%, 0 (I) spin, 0 (µ/µ_N) NMM}.

This theory ^{1, 2, 3} proposes that the relative abundances of the unusual, uncommon nonprimordial isotopes have changed in food supplies of plants, animals and humans such that humans have increased levels of the nonprimordial stable isotopes (²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and ³³S) in their cells during the last 150 years for increased prevalence of cancer. The technologies of the industrial revolution, nuclear reaction uses and industry, agricultural changes, automobile technology and radio-technology are proposed by this theory ^{1, 2, 3} to increase nonprimordial isotopes and even redistribute isotopes into key chemical bonds in biomolecules. By the author’s theory ^{1, 2, 3} for instance, radiowaves are able by broad band excitations to stimulate the continua states by the author’s theory ^{1, 2, 3} to redistribute nonprimordial isotopes into specific chemical bonds even in normal relative abundances relative to distributions in the absence of radiowaves. Thereby with increase enrichments, the radiowaves compound the clumping of non-primordial isotopes into specific chemical bonds in proteins, RNA and DNA. Technologies introduced all these new ingredients and conditions of nonprimordials, RF and microwaves and static magnetic fields (B_ext) to explain origin of cancer and acceleration of cancer.

These non-primordial isotopes reversibly, fractionally fiss and fuse to momentarily transmute to different quantum fields about the nuclei in atoms and molecules relative to the reversible, fractional fissing and fusing of primordial isotopes. Moreover, on the basis of this theory ^{1, 2, 3}, the author has determined that the fractional, reversible fissing and fusing of the nonprimordial isotopes are more sensitive than nuclei of zero NMMs to tiny intensity surrounding fields of thermal space as by Little’s Rules 1, 2 and 3. Such reversible, fractional fissing and fusing of the stable isotopes by the author’s theory ^{1, 2, 3} alters the enzymatic dynamics along the reaction coordinates of protein, nucleic acid, lipid, and carbohydrate biochemical dynamics. The fractional, reversible fissing and fusing of nuclei release NMMs to surrounding electrons for ‘internal nuclear pressures’ to alter surrounding atomic orbitals and such altered atomic orbitals alter molecular orbitals and alter chemical dynamics, catalysis and enzymatics by the Little Effect: “spins alter orbitals during chemical reactions and orbitals altering spins”. The Little Effect not only involves e^- spins altering orbitals but nuclear spins and nucleon orbitals also alter electronic orbitals for relativistic nuclear Little Effect as manifested by these nonzero NMMs of nonprimordials relative to more null NMMs of primordials.

For instance, the fractional, reversible fissing and fusing of the nonprimordial isotopes in enzymes can alter the stereochemistry of the substrate as the enzyme catalyzes the chemical transformation of the substrate. For instance, ¹⁴N and ¹⁵N nuclear motions have different chiralities as ¹⁴N has positive NMM and ¹⁵N has negative NMM; so changing ¹⁴N to ¹⁵N by this prior theory (1-3) would cause the fractional fissed field of ¹⁵N (relative to native ¹⁴N in the enzyme) to alter the chirality of wavefunctions from the enzymatic catalyzing transition state of the substrate relative to such fissed fields from primordial ¹⁴N. As the biomolecules have specific stereochemistry and manifest chiral environment in healthy organisms, the altered chirality can be a basis of disease as caused by ²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg. These alterations by the author’s theory ^{1, 2, 3} transform normal cells to cancer cells. Such altered chemical dynamics by isotopic replacements in DNA, RNA and proteins are manifested by the accelerations of cellular reproduction, replication, transcription and protein translation with consequent acceleration of the glycolysis process and the suppression of the Kreb cycle.

On the basis of the author’s theory ^{1, 2, 3} the surrounding radiowaves and static magnetic fields of technologies accelerate such faster glycolysis and slower Kreb cycle. Alterations of DNA reproductions, RNA transcriptions and protein translations cause cancer. The author further notes that both technologies for more nonprimordials and technologies for more external RF, EM radiations and static magnetic fields in combination cause more cancer and continued acceleration of cancer during last 150 years. But the author notes here just as nonprimodials can affect biomolecules in normal cells to cause cancer these nonprimordials can also affect cancer itself to kill cancer and with B_ext and RF such use of nonprimordials to heat and kill cancer cells is enhanced. The author in this paper uses proanthocyanidins as in skin of fruit and grape seeds as natural sources of ¹³C, ¹⁵N and ¹⁷O enriched polyphenols (nucleotides-like structures) to more strongly interact with cancer DNA in deadly ways (relative to normal DNA). Proanthocyanidins (PACs) are polyphenol compounds. Some foods are rich in PACs: blueberries, grapes, cranberries, cinnamon bark, hazelnuts and chocolate. Polyphenols are organic molecules having many phenol units. In this work the authors, determine similarity of polyphenol structures nucleoside structures in G, C, A, U and T nucleotides can cause favorable interactions and binding between the polyphenols of PACs and nucleotides in DNA. It is thought that the intrinsic nonprimordial bond-specific enrichment in PACs and the bond specific enrichment of nonprimordials in cancer DNA may cause stronger interactions of PACs with cancer DNA to alter cancer genetics and metabolism for use of PACs for treating cancer. The author notes the cancer already has ¹³C, ¹⁵N, ¹⁷O in its DNA and RNA and proteins. The proanthocyanidins have structures and ¹³C, ¹⁵N and ¹⁷O enriched in specific bonds to bind the causer DNA/RNA in stronger ways.

The observed mass spectra of the DNA of normal and cancer cells and the displacements of the peaks in the range 400 Da to 1000 Da may be interpreted on the basis of the fragmentations of the DNA into nucleosides, nucleotides and oligonucleotides during MALDI mass analysis process with varying characteristic isotopic compositions of ²D/¹H, ¹³C/¹²C, ¹⁵N/¹⁴N, ¹⁷O/¹⁶O and/or ²⁵Mg/²⁴Mg within the fragments. The C to T → U and A → G has methylations, dehydrations, deaminations and hydrations of rings of aromatics, purines, pyrimidines and ribose rings and phosphate groups as isotopically exchanged functional groups. On the basis of these varying isotopic compositions of the DNA in cancer and normal cells, the differing fragmentation patterns of the DNA can be reasoned. The varying isotopic contents can also be reasoned by different interactions, formations, replications, transcriptions, and translations of these nucleic acids in normal cells verses cancer cells.

The 429 Da peak may be enriched in nonprimordials in cancer due to adenosine diphosphate and its formation from guanosine diphosphate by dehydrations and deaminations of G; and aminating the intermediate may thereby result from faster functionalizations and defunctionalizations of ribose and pyrimidine rings by methylations and deaminations for thymidines having ¹³CH₃. See Figure 3. The normal cells have more local peaks about 429 Da relative to cancer 429 Da peak as cancer has more clumped nonprimordials. So the 429 Da nucleotide with nonprimoridial 17O in cancer DNA rapidly loses functional group; so the 429 Da peak is less present, but the fragments in the cancer having primordial ¹⁶O show larger peaks as they fragment less by loss of their ¹⁶O. ¹⁷O is more labile than ¹⁶O. The formation of the 429 Da from the 445 Da for G → A involves deaminations and dehydrations of G then aminations to A. The cancer cells have nanowater with ¹⁷OH₂ and ¹³NH₃ to complex the OH and NH₂ of G in cancer to convert to G* with ¹⁵N and ¹⁷O replacement in cancer G*. The ¹⁵N and ¹⁷O more readily undergo nucleophilic aromatic substitutions by ¹⁴N to form the A from the G by this theory ^{1, 2, 3} to explain the data. The clumping of nonprimordials in cancer DNA and G nucleotide may accelerate the deaminations and dehydroxylations of G as cancer has ¹⁵NH₂ and ¹⁷OH, which are poor nucleophiles and good leaving groups due to their negative NMMs. The ¹⁵NH₂ is a stronger nucleophile than ¹⁷OH as ¹⁵N has a less negative NMM than ¹⁷O; so ¹⁵NH₂ is expected to be harder than ¹⁷OH. ¹⁵NH₂ is expected to be a better nucleophile than ¹⁷OH for replacing ¹⁷OH of G* to form ¹⁵NH₂ of A*, so the ¹⁵NH₂ is harder base and should attack the purine rings faster than ¹⁷OH weaker nucleophile. Thereby cancer DNA should readily transform G*→ A* for unusual mutations. It may be that cancer cells show excess of adenosine and deficiencies of guanosine so this may reflect in anomalous RNA transcriptions and protein translations in cancer anabolism. Red blood cells show similar isotopic distributions relative to normal cells as the thymidine and cytidine may not functionalize their ring with ¹⁷O as ¹⁷O defunctionalizes from guanosine.

Figure 3.Purines

The unusual enrichments in the 445 Da peak of cancer with nonprimordials (relative to 443 Da for primordial G) may be explained by the A* in the 429 Da peak of A* as the A may reversibly undergo uphill slower process of deaminations, hydroxylations and aminations to form the G at 445 Da peaks. Thereby the clumped nonprimordials in G more accelerate the loss of ¹⁵NH and the gain of ¹⁵N and ¹⁷O to form A, relative to primordials in A of normal cells to form the nonprimordial G in the cancer. So the peak at 445 Da peak is nonprimordial enriched in cancer DNA as the nonprimodials compose A, leaving the nonprimordial enriched G at 445 Da peak rather than 443 Da. See Figure 3. Cancer DNA at 445 Da is heavier with nonprimordials relative to normal white cells DNA. Vice versa in the cancer cell the G* may transform readily due to its clumped nonprimordial isotopes transform to A*. The dehydroxylations and deaminations and aminations of the G* in cancer DNA are accelerated due to the negative NMMs of the ¹⁵N and ¹⁷O for alterations of leaving ability in the dehydroxylations and deaminations. But the aminations to form the final A* is expected in cancer DNA as the ¹⁵NH₂ is a weaker base and weaker nucleophile than ¹⁷OH due to the harder basicity of ¹⁵NH₂ relative to ¹⁷OH and due to the less negative NMM of ¹⁵NH₂ relative to more negative NMM of ¹⁷OH^-. The hydrogens also help harden the ¹⁵NH₂^- as there are more H in ¹⁵NH₂ relative to ¹⁷OH. Stronger internal magnetism to stabilize ¹⁴NH₃ verses ¹⁵NH₃ has greater stability of ¹⁵NH₃ so ¹⁴NH₃ goto N₂ + H₂ faster and stronger bonds. ¹⁵N triple bond is less stable. ¹⁴N triple bond may be easier to break. So breaking ¹⁵N₂ may be easier than breaking ¹⁴N₂ and the stability of ¹⁵N-R in organic compounds may be greater than ¹⁴N-R toward N₂ formations.

So the heavier U (484 Da), T (482 Da) and/or C (483 Da) in cancer couple by chemical transformations to 502 Da of U* (methylated U) in cancer by methylations (¹³CH₃, 16Da); by U* dehydroxylating to form T* (with ¹³CH₃, 16Da); by U* dehydroxylating (¹⁷OH, 18Da) and aminating (¹⁵NH₂, 17 Da) to form C*. See Figure 2. Such many possible dynamics manifest nonprimordial accelerated functionalizations and defunctionalizations in cancer cells relative to normal cells and the resulting nonprimordial induced chemical transformations of U → U*, U* → T* and/or C* → U* for new mechanisms of mutations of DNA and RNA as here disclosed as by not only by changing isomeric connectivity along chains but also by interchemically converting nucleotides of U, T and C! Such complex inter-chemical conversions are observed in the mass spectra of the cancer relative to the normal cells. So the normal cells have finer peaks in this range 400 - 409 Da. The cancer DNA less fragments to form U, T, and C and have less fine spectra due to nonprimoridials clumping from 400 to 409 Da. The nonprimordials (¹³CH₃) in the cancer nucleotides may cause less fragmenting of cancer DNA for fewer of these peaks from 400 - 409 Da. The normal cells have random methylations, the random methylations of C and random ¹³CH₃ in C, T, and U can lead to such fine peaks in the normal cells. But the cancer cells have nonrandom, clumping of ¹³CH₃ and ¹⁵NH₂ and ¹⁷OH and the ¹³CH₃ causes stronger binding of the cancer DNA for less fragmentations under electromagnetic fields in mass spectrometer. There is more 483 Da in cancer DNA and there is more 484 Da in normal DNA, there is more T* in cancer DNA and more C* in normal DNA. These trends for cytidine, uridine and thymidine triphosphates are consistent with the peaks at 400-409 Da for the diphosphates as the diphosphates also revealed less T to C for cancer DNA. The T* → C* conversions in cancer would involve the dehydroxylations of pyrimidine and hydroxylations of ribose and the aminations of thepyrimidine. The negative NMMs of the ¹⁷OH and ¹⁵NH₂ in cancer make this less likely. As the negative NMM of ¹⁵N and ¹⁷O make ¹⁵NH₂ better nucleophiles for the conversions of the pyrimidine to C* in cancer DNA but instabilities. The cancer DNA thereby less expresses C* at 483 Da.

The 487 Da is from the dehydroxylations (¹⁷OH or ¹⁸OH ¹⁷O²D or ¹⁸O²D of 18 Da to 20 Da) of ribose in adenosine triphosphate at 507 Da. See Figure 3. In normal cells, the dehydroxylations are more than in cancer cells as the cancer cells have more ¹³C in the ribose, which bind the ¹⁷OH more strongly. So cancer at 507 Da should be heavier. But cancer is observed not to be heavier at 507 Da as the 507 Da is coupled to 523 – 525 Da by dehydroxylations. So 523 Da to 525 Da of G* in cancer losses ¹⁷O (rather than ¹⁶O) to cause less massive peaks at 482 Da. Cancer hydroxylates better if it is heavier (clumped with ¹³C or ¹⁵NH₃), so the 507 Da peak in cancer lacks heavier nonprimordials as they are loss of ¹⁷OH from 523 – 525 Da to G*. So they are missing 507 Da peak A* at 525 Da peak in G*. This conversion of nonprimordial G* to nonprimordial A* in the cancer DNA is expected as the G* to A* involves the deaminations, hydroxylations and aminations of the purine. The cancer having clumped nonprimordials may accelerate this as the ¹⁵NH₂ and ¹⁷OH in the cancer DNA are weaker nucleophiles (due to their negative NMMs) relative to ¹⁴NH₂ and ¹⁶OH. But in principle ¹⁵NH₂ and ¹⁷OH should be poorer entering groups due to their negative NMMs but ring ¹⁵N can pull in the ¹⁵NH₂ and ¹⁷OH nucleophiles. It is observed that cancer is heavier at 525 Da G* relative to normal cells being lighter at 523 Da. As the 523-525 Da is guanosine triphosphate and the ¹⁷O on the guanosine triphosphate stabilize the ¹⁷O and the ¹³CH₃ for less massive peaks at 505 Da and less massive peaks 487 Da in the cancer DNA samples due to losses of heavier ¹⁷O and ¹³C, respectively. So this is general principle when ¹⁷O is active in fragmenting, the daughter peaks are enriched in less massive than peaks in primordial normal DNA. When ¹³CH₃ is active in the fragmenting the daughter peaks are enriched in nonprimordials as the ¹³CH₃ fragments stabilize by ¹³CH₃ with consequent heavier daughter peaks. The nonprimordials in the ¹⁷OH destabilize and the ¹³CH₃ stabilizes primordials. So the enrichments in the daughter by primordials are actually due to lack of instability or less fragmenting of nonprimordial than primordials.

All + or – NMMs activate bond breaking. All – NMMs have faster kinetics of bond breaking to cause new effects relative to all + NMMs. Faster kinetics can lead to different product distributions and breaking stronger bonds. All negative NMMs may break C-C, C-O, C-H, O-H bonds and all positive break C=C ⟷ C-C The activated state may then better bond back together by + NMMs + +NMMs with faster rates and with more thermodynamic stability. Such may be more discerned under conditions of high temperature, strong electric fields, strong magnetic fields and/or high pressures. The π bonds in DNA and RNA makes it easier to alter by NMMs, explaining why reproductions, transcriptions and translations are more affected by nonprimodials relative to glycolysis and Kreb cycle. Amino acids having π bonds like tyrosine and phenyl alanine (C=C) may more easily be affected by nonprimordials. Aspartate and glutamate have carbonyl side groups with resonating pi bonds. But amino acids have C=N and C=O and C=C but not aromatic. Carbonyls have resonating C=O.

The 506 Da and 507 Da peaks can also be explained on the basis of their A contents. It can be that guanosine triphosphate at 523 Da peak loses ¹⁷O to form 507 Da peak {which corresponds to adenosine triphosphate} and the clumped nonprimordials help loss of ¹⁷O to explain the patterns. G → A. See Figure 3. The nonprimordial G at 525 Da peak more rapidly loses ¹⁷O to produce more than 50% greater loss than ¹⁶O is lost to produce 507 Da in the cancer. Thereby here it is proposed that nonprimordial isotopes epigenetically alter nucleic acids in cancer by causing G →A. The 523 Da peak may involve transformations between A and G with a surrounding peak; so that in cancer there is peak enrich in primordial isotopes. A → G by hydroxylations, deaminations, and aminations. G → A by dehydroxyations, deaminations and aminations. Ammonia in tumor can encourage aminating and deaminating G and A, and also induce C → T.

The AT fragment associated with the 669 Da to 671 Da peaks and T in AT may be the reason the cancer DNA is enriched in nonprimordial isotopes as the T may form from ¹³CH₃ methylations of cytosine and the cytosine may undergo deaminations and dehydroxylations or the C may → U by deaminations and hydroxylations under acidic conditions as in altered nucleuses (isotopic replacements) as nucleuses are more basic than cytoplasma. The more basic nucleus in cells stabilize T and U as T is more basic and nonpolar relative to U. So in cytoplasma, the T → U as the more acidic cytoplasma can push out ¹³CH₃. It is quite interesting that AT are detected as in cancer AT are thought enriched and GC are thought deficient in cancer. Again in the cancer the accumulations of nonprimordial T* are observed as the T* cannot (due to clumped nonprimordials) convert to C* as the conversion of T* would require demethylations (loss of ¹³CH₃). The ¹³CH₃ is a strong base and good nucleophile and the cancer cells cannot as well lose ¹³CH₃. The heavier 675 Da peak in cancer is due to ¹³C and its ¹⁷O.

The 680 Da and 681 Da peaks may be explained by isotopic distributions in GC or GT. The 680 Da and 681 Da peaks of normal cells are enriched in primordial isotopes as by the T and C having more ¹²CH₃ and ¹⁴N₂; but the cancer DNA is enriched in nonprimordials at 681 and 682 Da peaks due to the isotopic clumping of nonprimordials to enrich the ¹³C methylation of C to form ¹³CH₃ in T* also having ¹⁵N. There is more GT in cancer than normal cells. There is more GT in cancer than AT. GT has stronger binding due to the 3 hydrogen bonds relative to only 2 hydrogen bonds in AC. G is deficient, so why so much TG? Although deficient G binds strongly to T. Again the enrichments of ¹³CH₃ in T* in nonprimordial cancer is detected and the inability to convert T* to C* in the cancer increases T^*. Red Blood Cells are enriched at 682 Da peak relative to cancer at 681 Da peak and this could be due to ¹⁷O in G, C and T in the red blood cells as the red blood cells couple to air for ready oxygenation. It may be possible to relate cancer to ¹⁷O from the air as well as ¹⁷O in the water. So the blood can accumulate ¹⁷O from ¹⁷O₂ and H₂¹⁷O and ¹³C¹⁷O. The red blood cells are different from white blood cells. The red blood cells may be a basis for the cancer spreading the ¹⁷O to normal cells.

The unusual enrichment of primordial isotopes in cancer AG at 695 Da and 697 Da peaks may be reasoned on basis of G content in GA and the cancer may have ¹⁷O and ¹⁵N on guanosine and many normal cells have less ¹⁷O and ¹⁵N on guanosine. There is observed that there is less GA in cancer DNA than GT or GA fragments less than GT. Less observed GT is consistent with the discovery of transforming G to A in cancer genesis by this work. But the observed greater 695 Da relative to 697 Da in cancer may be explained by this theory. So the ¹⁷O is more rapidly lost from guanosine of cancer DNA relative to less lost of ¹⁶OH from guanosine for the greater 695 Da peak relative to 697 Da peak for cancer. The 695 Da may be coupled thereby to 695 Da+ 14 Da = 709 Da peak or the 695 Da + 9 Da = 703 Da. This 703 Da peak should be enriched in clumped nonprimordials in the cancer as by loss of O^2- from G or A. The 14 Da may be loss of 14 Da or NH₂ – from G or A. The cancer DNA shows both 703 and 709 Da peaks and manifest this clumping. But the normal cells do not show such peaks at 703 Da and show a small peak at 709 Da in support of this reasoning. The guanosine may be more reactive due to ¹⁷O relative to ¹⁵N as the ¹⁷OH is stronger nucleophile than the ¹⁵NH_3; and NH₃ is less abundant in normal cells! It seems in general ¹⁷O helps decompositions and fragmentations. The ¹⁷OH₂ and ¹⁵NH₃ in surrounding nano-water in cancer cells may accelerate exchange of ¹²NH₂ and ¹⁶OH by ¹³NH₂ and ¹⁷OH. Scientists have not measured ¹⁷O in mass spectra and NMR enough to see this effect of ¹⁷O as determined in this work. Most prior work on O has focused on ¹⁶O and ¹⁸O. The complexations of this biomolecules by ¹⁷OH and ¹⁵NH₂ cause softening of the bonds for faster substitution and replacement reactions due to the negative NMMs of ¹⁷O and ¹⁵N.

So in general where ¹³CH₃ reactions are accelerated in cancer, the methylation consistently shows heavier peaks in cancer DNA and its pieces. But where ¹⁷OH and ^15NH2 are involved the aminations and hydroxylations consistently show smaller masses in the mass spectra of cancer DNA and its pieces. The larger massive pieces during methylations result and are explained by the addition of more massive ¹³CH₃ into the functional of DNA nucleotides. The less massive pieces during aminations and hydroxylations are explained as resulting from loss of more massive ¹⁷O and ¹⁵N from the functionals of cancer DNA and its nucleotides. In general, the ¹³CH₃ and its positive NMMs strengthen the covalent bonds in cancer DNA for binding ¹³CH₃ is a stronger nucleophiles for more rapid replacements in DNA and its nucleotides. But the ¹⁵NH₂ and ¹⁷OH and their negative NMMs weaken the covalent bonds in cancer DNA for bond breakages and ¹⁷OH and ¹⁵NH₂ are better leaving groups for more frequency of ¹⁵N and ¹⁷O of nucleotides under electromagnetic fields during NMR analysis to explain these observed mass spectra.

It may not be that ¹⁷O and ¹³C attract or repel by internal C frame magnetism. It may be that they self conform to form quanta. So all + NMMs → classical or all – NMMs → classical, but balanced + NMMs → and – NMMs → quantum and the monopoles separate locally but bind globally. So on one scale they may bind and on larger scale repel or vice versa. So ¹⁴N drives biomolecules by imbalance perturb e^- e^- quanta ¹⁵N may disrupt such natural imbalance of ¹⁴N; ¹⁷O also disrupts the ¹⁴N imbalance; ¹³C disrupts e^- e^- quantum mechanics; and ¹⁴N cannot help ¹³C. But ¹⁷O can help ¹³C at higher temperatures, in electric fields and magnetic fields. But ¹⁵N can help ¹³C at higher temperature, in electric fields and magnetic fields. ¹⁷O disrupts ¹⁵N quantum mechanically, but together they help pull in ¹³C and less ¹⁴N causes loss of protein nuclear perturbation. On such basis the author notes tumors may be killed by enriching ¹⁷O, ¹⁵N, and/or ¹³C in their biomolecules and exposing them to strong electric fields and/or strong magnetic fields. ¹³C may overdrive classical mechanics of protein with ¹H and ¹⁴N. ¹³C causes accelerated glycolysis as driven fragmentation of glucose. But the combining of C to O is opposed by ¹³C and ¹⁴N in the Kreb cycle or they oppose sp³→ sp, sp². + NMMs favor sp³, - NMMs favor sp and sp² for ¹³C but not for ¹⁷O. So ¹³C favor sp³ and ¹⁷O favor sp³ (for different reasons) as higher e^- e^- density for ¹³C increase electron density on C and less e^- e^- repulsions for negative NMMs of ¹⁷O reduces electron repulsions about O. So ¹³C and ¹⁷O accelerate glycolysis by one environment. But ¹³C and ¹⁷O suppress the Kreb cycle as in the Kreb cycle the sp² and sp hybridizations are catalyzed about C and O and the ¹³C and ¹⁷O oppose such sp and sp² hybridizations but favor sp³ hybridizations. But ¹⁷O and ¹³C decelerate Kreb cycle by different environments.

In this work, the author proposes a new way to alter functional groups of uridine, thimine, cytosine, adenine and guanine (by isotopic substitutions/replacements of ^!H, ¹⁶OH, ¹⁴NH₃, ¹²CH₃, and ²⁴Mg by nonprimordials of ¹⁷OH, ¹⁵NH₃, ¹³CH₃, ²D and ²⁵Mg) as nonprimordial, functional groups entering and to replace primordial, functional groups of nucleotides by this new theory as by the many aromatics of the purines and pyrimidines oscillating their electrons to couple the many nonzero NMMs of these nonprimordial, functional groups for activating their nucleophilic substitutions of primordial, functional groups. The theory ^{1, 2, 3} introduces novel chemical dynamics of multiple electrons and multiple functional groups in nano-domains behaving nonclassically to couple their spins and electronic motions to violate the 2^nd Law of Thermodynamics momentarily as energy is focused into specific fewer atoms of the group to catalyze transportations, transformations and momentary transmutations for novel chemical dynamics of many bodies as the nanodomains by this theory gets quantum mechanically into a single atom or small molecule by Little Effect the fermionic atoms by their nuclei (NMMs) are in analog to fermionic electrons in atoms. By such the atoms in the domains have a wave natures and they exchange and correlate to move and alter their wave natures and they exchange and correlate to move and alter motions and positions in the nanosolution so as to lower energies. But for biomolecules such waves are quantum waves and differ from larger classical waves as by the theory ^{1, 2, 3}, the nano, subnano waves can superposition to focus intensites in to specific bonds for quantum activations and this explains novel bond activations by enzymes. Such motions and altered positions manifest new chemical changes of the atoms, small functional groups in the nano-domains of proteins, nuclei acids and nanowater and nano-ammonia. So that the biochemical transformations have been previously described by the author as nanoscale quantum wave mechanics that manifest at lower temperatures for fermionic nuclei having nonzero NMM, but higher temperatures and pressures and E, B can induce the quantum wave mechanics of nanosolutions composed of null NMMs.

So inside the nucleus, GATC are the nucleotides; but outside nucleus GAUC are the nucleotides. Methylations (¹³CH₃ ) of U cause T*. So isotopic effects in cytoplasma get into nuclei by U + ¹³CH₃→ T* in cytoplasma and transfer of T* into nucleus. So ¹³CH₃ on T* in nucleus causes altered genetics as reasoned by this theory. In prior work, it was previously published U expresses as T* due to ¹³CH₃. So ¹³CH₃ seems like H (by their positive NMMs); so T* becomes as U; and U in nucleus alters genes. Normally U is in cytoplasma and T is in the nucleus. So by U → U* → T*,U^* is transport into the nucleus via T*, the replication of DNA is altered by such U* and T^* in the nucleus of cells as ¹³CH₃ (methyl) on the thymine alters biochemical dynamics. Also ¹³CH₃ in T* may accelerate T*→ C* by dehydroxylations, deaminations, and aminations. So this causes mixing of nucleotides and mutations by chemically interconverting of nucleotides. T → U. U → C. Such chemical transformations of nucleotides alter the genetic code to cause cancer and other diseases. This theory ^{1, 2, 3} further proposes that the external static magnetic fields and radiofrequency fields can excite these nanosolutions to accelerate these nonprimordial substitutions. It may be that such chemical transformations of nucleotides in normal cells to mutate normal cells to cancerous cells are kinetically and thermodynamically possible by a few nonprimordial substitutions; but with more and more nonprimordial substitutions, the replacements are slower or not allowed. Such chemical transformations may occur as normal cells transmute to cancer cells with higher amounts of NH₃ in the cancer environment. But this theory proposes that the use of external magnetic fields for stimulating cancer cells so their DNA pull in more nonprimordials so the excess nonprimordials kill the cancer. With such rapid replications of cancer DNA, it should be easy to disrupt the genes in cancer so the cancer cannot produce its proteins for glycolysis to kill the cancer.

Adenine is unique as it is the only nucleoside lacking O group and has only N functionals. The N is weaker base and weaker nucleophile than O as in guanine, uridine, thymidine and cytidine. It is on this basis of RBL that the ¹⁷O in water is the basis for the enrichment of ¹⁷O in DNA and RNA. The ¹⁷O in the many rings help the ring pull in ¹³C as by ¹⁷O activating bond cleavage of ¹⁷OH and + NMMs but many ¹⁴N, ¹H and ³³S and other ¹³C can induce, new bond formations, but as excess + NMMs cleave + ... + NMMs bonds and excess – NMMs cleaves - ... - NMMs bonds in quantum fields. So quantum fields + … - NMMs globally bond and + ... + NMMs locally agitate bonds and - ... - NMMs locally agitate bonding and as the nonprimordial isotopes clump they manifest new enzymatics of the DNA and RNA. . So this theory ^{1, 2, 3} introduces totally new chemical dynamics as here it is determined novel nonlocal chemical bonding but local chemical decomposition and/or nonlocal chemical decomposition but local chemical bonding.

The patterns of null, + and – NMMs (needles in haystack) can cause local bonding while globally the fermions are unbound. So the theory ^{1, 2, 3} determines that systems of + and – NMMs (Nuclear Frames) bind the atoms globally on large scales as they locally repel and are chemically broken. This is why ¹³C and ¹⁷O and ¹⁵N activate transition states and lower the barrier to chemical substitutions of isotopes. But the theory ^{1, 2, 3}, the + and - NMMs as are more common in our sector of the Universe (or in other sectors – and - ) locally on nuclear scales repel but on global scales they bind/attract. So this also in other sectors of Universe with – NMMs have – NMMs interacting with – NMMs repel locally in nuclei but bind to attract globally as in Ag nanoparticles and other rare elements having all – NMMs. But such considerations, RBL gives a totally new model for transportations (superconductivity) and transformations {chemical and biological dynamics}. So prior chemistry and transport have focused primarily upon + ... + NMMs and the globally binding by e^- e^- and the locally repelling /unbinding by NS Frames with less chemistry and transport possibilities. Such manifest in primordial nanosolutions in cells having + NMMs of ¹⁴N, ¹H and ³¹P and null nuclear magnetic moments (NMMs) of ¹²C, ¹⁴N, and ¹⁶O and normal primordial biology manifest on such basis of repulsions on NS Frames and motions and biochemistry of binding on L frames of wavefunctions. But RBL introduces totally new effects of – NMMs + ... + NMMs binding locally in NS Frames and repelling globally in L frames. So bonds are broken globally to isolate the e^- e^- but locally the e^- e^- bind by the + NMMs and – NMMs to manifest a Reggie Pair bond by NMMs of + and – NMMs as this occurs in nanosolutions in cells as ¹⁷OH₂ and ¹⁵NH₃ enrich with ¹³CH₃ in the nanosolutions, proteins and nucleic acids. So the nanosolutions bind on NS Frames but globally the e^- e^- are more broken chemically. So the proteins and nucleic acids have different motions, binding enzymatics and biochemical reactivity. Such theory explains the cancer cell as the protein ··· nucleic acids interactions are altered by the + and – NMMs causing wavefunctions to repel. But the nuclei still pin the atoms together for cancer habitat.

It is important to consider that by such model of theory ^{1, 2, 3}, in normal cells the ¹⁴N and ¹H can modulate the bond cleavages and bond formations of PO₃^- and the ribose as the compressions may induce bond cleavages of ³¹PO₃^- to release energy and the chemical composition of ribose (of null NMMs). As compressions break + NMMs of PO₃^-, but bind C-C-O-H of ribose of O (null) NMMs. But then the rarefaction binds PO₃^- and fractional fissings and fusings decompose ribose and these can couple to pull apart base pairs or also such dynamics couple to surrounding proteins to bind or decompose the proteins to pull in or push out proteins. And such can explain DNA replications quantum mechanically as bases recognize quantum mechanically by patterns of NMMs and compress/rarefy with pulling in and pushing out. And likewise for transcriptions. And in ribosomes such act vice versa as pulling in amino acids under conditions whereby the oligonucleotides, RNAs are stable.

The clumping may help ¹⁵N incorporations into the oligonucleotides. The functional groups can dynamically shift the functionals to find equilibrium with the kernelling of nonprimordials, lowering the energy relative to random distributions of the nonprimordials in normal cells. Such clumpings of dense regions of nonprimordials isotopes alter nuclei acid bindings, bond strengths and chemical stabilities as by enzymatic actions on the kernel regions. But the clumps in normal cells may be linked to noncoding regions of DNA. So later the oligomers of food tannins can modify the functionals in cancer cells more than in normal cells to kill the cancer cells!

The guanosine may be more reactive due to ¹⁷O relative to ¹⁵N as the ¹⁷OH is better nucleophile than the ¹⁵NH₃ and ¹⁵NH₃ or ¹⁴NH₃ is less abundant in normal cells! It could be that the presence of ¹⁴NH₃ causes the genetic alterations of normal cells to cancer cells and the ¹⁵NH₃ helps as by mutating genes. Comparing the various signals, the FWHM of signals from fragmented DNA in normal cells appear broader relative to the signals of fragmented DNA from cancer cells (note that this points to clustering of nonprimordials in cancer DNA and this narrow FWHM of cancer DNA is consistent with clustering of nonprimordials to dense kernels in the cancer DNA). The smaller FWHM in cancer DNA fragments may be near and from the clumping of nonprimordial functional groups of deuterons, hydroxyls, amines, and methyls. Such clumpings of nonprimordials lead to sharper distinct fragmentations during the mass analysis of DNAs for sharper peaks relative to broader peaks in fragmenting of the primordial regions of normal DNA. By the theory, the incorporation of nonprimordials of ²D, ¹³C, ¹⁵N, ¹⁷O and ²⁵Mg into cancer DNA by functionalizations and defunctionalizations of the nucleotides appear to explain these observations of DNA isotopic differences between cancer and normal cells. It is important to note that the easier fragmenting of these pieces having nonprimordial isotopes in cancer cells relative to less sharp fragmenting in normal cells is evidence of altered interactions of nonprimordial isotopes in the DNA and RNA for altering the replications, transcriptions and translations.

So after considering these different causes of the functional groups in cancer and in normal cells on the basis of based on the spectra, a discussion of the proclivity of nucleotides and oligonucleotides to the new chemistry is next given. The aromatic and the ring structures by the theory ^{1, 2, 3} previously modelled such biomolecules on the basis of Na⁺ and K⁺ interactions with graphene oxides. It was determined that Na⁺ and K⁺ NMMs interact favorably with graphene oxides with their sp² and sp³ mixed hybridizations and magnetics via the nonzero NMM of K⁺ and Na⁺. Thereby, likewise, RBL reasoned similar NMMs interact with sp² and sp³ networks but now in biomolecules like DNA. So that the theory ^{1, 2, 3} introduced changes in interactions in the DNA as primordials of ¹H, ¹²C, ¹⁴N, ¹⁶O, ²⁴Mg, and ³²S are replaced by nonprimordials of ²H, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg, and/or ³³S of different NMMs. Such manifest as the purines and pyrimidines in nucleic acids regions with sp² aromatic and regions with sp³ nonaromatic in analog to prior different regions in graphene oxide.

Thereby the theory ^{1, 2, 3} realized nuclear spins could couple to carbon covalent dynamics in prior graphene and in biomolecules. But even before the experiment with graphene oxide the spin interactions and NMMs of p⁺ interacting with biomolecules had been published in a book Chapter ². So by considering graphene an analog for proteins and other biomolecules. The theory ^{1, 2, 3} proved that nuclear spins in general can couple to biomolecules to alter catalysis and enzymatics of biochemical reactions. Next in this work, the mechanism by Little’s Effect are given for driving the replacements and substitutions of null NMMs by nonzero NMMs. The more extended aromatic rings may couple spins of the nuclei for faster clumped, accelerated isotopic enrichments of the ring systems via the aromatic π electrons as the aromatic electrons couple the separated nuclear magnetic moments (NMMs) and induce transports, exchanges and replacements of the different NMMs. These extended π electrons and orbital exchange and bonding about many atoms may be mechanism for more strongly coupling the nuclear spins and NMMs {Reggie Acids and Bases of electron radicals (fermions) and nuclear spins (fermions) and nuclear radicals and orbitals} to orbitals (of Lewis Acids and Bases, both electronic and nucleonic) via the exchange by π electrons. The nuclear spins and the nuclear orbital angular momenta are thereby exchanged and coupled via delocalized π e^- e^- in the phenyls, polyphenols, and polyphenylamines. Also by this model ^{1, 2, 3}, such spins are not limited to e^- spins; nuclear spins are also coupled, transformed, transported and transmuted by π e^- e^- and d orbitals of transition metals. By the model ^{1, 2, 3}, the substrates couple and quantum mechanically exchange the NMMs in the enzymes and macromolecules and vice versa.

The localized bosons, the localized fermions, the delocalized bosons and delocalized fermions may be driven by surrounding thermal perturbations, gravity, electric, magnetic and QF driving forces. The relative stabilities and interactions for stable ferromagnetism, paramagnetism and diamagnetism are by Little’s Rules as diamagnetism in such systems may obey Little’s Rules 1 and 3 but ferromagnetism, antiferromagnetism and paramagnetism in such systems may obey Little’s Rules 1 and 2. The diamagnetism may be by the bosons localized as in diamond, but in graphene the bosons are delocalized bosons. Such happens in graphene to cause electronic spin paired fermions in the delocalized electrons. These unpaired delocalized fermions cause the delocalized to rehybridized to localized as sp² to sp³. The theory of RBL determines some transient spin induced, finer, azimuthal, fractional, continua quanta numbers for transition stages during transportations and transmutations. And likewise with the nuclei, as the nuclei interact with the electrons and bosons in graphene the nuclear spins and orbitals angular momenta in nuclei alter the electronic delocalization for singlet to triplet on other spins. The fractional fissings and fusings of nuclei seep QF into electronic shells as by the theory ^{1, 2, 3}, so as to transiently create ultrafine continua of azimuthals for mixing, coupling, transporting, transforming and transmuting electrons for novel superconduction, chemistry and catalysis/enzymatics. Vice versa e^- e^- rehybridizations and spin polarizations can alter the couple nuclear orbital momenta by RBL Effect. The localize bosons verses delocalized bosons allow different coupling of nuclei and their NMMs. The thermodynamics may favor one or the other, but the change from one to other involves kinetics and dynamics by Little’s Effect. The e^- spins and nuclear spins via delocalized or d (azimuthal) π e^- e^- can couple to alter the symmetries and motions from locals to nonlocals and vice versa.

Pure metal clusters and nanoparticles may also couple nuclear spins. But in molecular compounds, the coupling may not be possible via more localized molecular orbitals. But the delocalized molecular orbitals via π bonds may afford the delocalized bonding over many C, N, and O bonds as previously proposed in theory (RBL ferrochemistry). So that the π electrons can couple spins and orbitals of electrons (e^- e^- Lewis pairs and radicals) and the π electrons can also couple the nuclear spins and nuclear angular momenta over many atoms in nanodomains. Thereby the pyrimidine’s aromaticity more exchange the nonprimordials. The purine’s aromaticity less exchanges the nonprimoridals. Just as for the pi electrons in purines and pyrimidines delocalize the NMMs of ¹³C, ¹⁵N, ¹⁷O, likewise the pi electrons in polyphenols and polyphenylamines delocalize these nonprimordial isotopes and their NMMs. The nucleotides, oligonucleotides and nucleic acids couple their nuclear magnetic moments (NMMs) with NMMs in surrounding nanowater and accumulated NH₃ to accelerate primordials replacements by nonprimordials by different NMMs. So the delocalized e^- pull in NMMs. These molecular orbitals can couple spins on centers. So also spins can alter orbitals and the orbitals can alter spin centers, spin ... spin orbital interactions not only alter orbits but flicker spins; transition states break bonds; spins flip and intervening metal orbitals and/or orbits couple spins to other regions when orbits change and spin pairs change polarizations to change bonds. By this mechanism ^{1, 2, 3}, the spins not only interact with the orbits, but the spins transform by fractional, reversible fissing and fusing. Fissed spins fractionally, reversibly fiss and fuse to orbits and vice versa the orbits fuse to spins. So also NMMs via e^- e^- orbitals can couple nuclear spins and change the orbitals. Nuclear spin momenta and orbital momenta can alter the e^- e^- orbital. And e^- e^- orbitals can alter nuclear angular momenta. RBL here notes NMMs are variable by not only during chemical reactions but also during chemical reactions, enzymatics, vibrations, optics and e^- e^- transportations and transmutations. The nuclei are perturbed so relative motions of nucleons change and the nuclei swell and compress for fractional, reversible fissing and fusing to alter and to couple to surrounding e^- e^- lattice. Thereby momentary changes in NMMs occur. The DNA and RNA have more pi bonds for easier activations by breaking pi bonds for easier replacing isotopes relative to other biomolecules. Therefore, it is this reason of the aromatic rings in purines and pyrimindines that the nucleotides in DNA more readily exchange isotopes nuclear spins and NMMs relative to other biomolecules.

It may be possible by such unique ability of DNA and RNA via their nanodomains of graphene, diamond, alkyl, aromatic and/or diamagnetic, paramagnetic ferromagnetic functional substances that the resulting DNA and RNA catalyze isotopic exchange in proteins. So that during DNA, RNA and protein bindings, interactions, charge exchanges and enzymatics, isotopes may be exchanged. By this theory, the ¹⁴N, ¹H and ³¹P via fractional, reversible fissing and fusing cause the denatured proteins to renature and the DNA to unnature and renature during reproduction, and RNA to denature and nature. So in general, the NMMs in the proteins and nucleic acids cause orbitals to change. So the proteins and nucleic acids denature and renature. So the proteins and nucleic acids renature so rapidly due to huge fields caused by the nonzero NMMs of ¹⁴N and ³¹P within them (and ¹H₂O in surrounding nanowater). Thereby from this theory the RNA may catalyze the nonprimordial replacements in amino acids as the RNA translates proteins.

The isotopic exchange is selective in uphill anabolism in animals and humans nonadiabatically as it is selective in uphill anabolism in plants adiabatically. It is during uphill processes of DNA replications, RNA transcriptions and protein translations that the proteins are isotopically altered. Virus RNA can modify so the RNA produces unhealthy proteins. It is that the side chain sugar and side chain phosphate couple energy into the nucleoside to break bonds. It is that the side phosphates and side sugars help the NMM replacements. This occurs by the ferrochemistry of the bond rearrangements of the sugar releasing energy reversibly as accumulations and absorbing into the phosphates by NMMs and other oligonucleotides by ¹⁴N and ¹H so as to give energy to promote the dynamics. So activated states near or far are involved and then as the transition states relax to products, the phosphates collect the energy and restore it back to the sugar unit. There is chemical energy in the sugar and the phosphate can store chemical energy and the nucleosides can delocalize energy. It is on this basis that some viruses can kill cancer cells. But the downhill catabolism (relative to uphill anabolism) is less affected by isotopic replacements as the electronic energy can drive and dictate the dynamics. But in glycolysis the down hill is accelerated by the isotopic replacements as downhill glycolysis is reverse of photosynthesis in plants so the downhill accelerated by nonprimordial ¹³C just as uphill is slowed by ¹³C. It is logical that exothermic downhill is less discriminating nonprimordial / primordial replacements. But in Kreb cycle, higher electric and magnetic fields in the substrates and the enzymes cause stronger effects on the downhill processes as the high fields can couple more strongly to the NMMs for the nonadiabatic Kreb cycle so that Kreb cycle becomes adiabatic as the heat is organized in the high fields. This is the reason the Kreb cycle is more sensitive to nonprimordial isotopes relative to the glycolysis process.

Thereby this theory determines that the DNA may accumulate the nonprimordials from the proteins and sugars combusting and then the DNA may incorporate the nonprimordial isotopes into the proteins during translations, replications and transcriptions for the nonessential proteins. The eating of nonprimordials in nonessential proteins can cause the animals to accumulate nonprimordials; first in nucleic acids and then in proteins via nonessential proteins. But as the organisms eat other animals and obtain essential amino acids, then the essential amino acids have more nonprimordials. So the nonprimordials within the eaten essential amino acids connect to alter catabolism in cancerous ways in the essential proteins. The ¹³C in lysine is crucial for animals and humans to develop cancer. So diet accumulate ¹³C in DNA and then diet of essential amino acids accumulate nonprimordials in enzymes. When the two conditions optimize then cells become cancerous. Cancer cells may accumulate nonprimordial isotopes until they die and then the innards with the nonprimordials of the dead cancer cells are eaten by normal cells and the the surrounding normal cells transform to cancer cells. This may be a basis for metathesis. RNA with the nonprimordial isotopes can synthesize nonprimordial amino acids and construct nonprimordial proteins. These with lysine can cause cancer.

More general discussion is given here of NMMs coupling by MOs and AOs causing nucleophile substitutions and NMMs undergo substitutions and replacements. Nucleophiles driven by nucleophiles but the spin driven by magnetism as the null spins diamagnetically pushed out MO and the nonzero spins pull in or push out MOs and AOs. But what about the + NMMs and – NMMs. The + NMMs pull in + NMMs and push out – NMMs in MOs and AOs. But in nuclei and continua + NMMs push out + NMMs and pull in – NMMs. So thereby ¹³C is pulled into other ¹³C via π bonds as the many ¹³C nuclei create self conforming MOs. But ¹⁷O disrupts MOs of ¹³C to activate bond rearrangements. As ¹⁷O pulls ¹³C nuclei together and yet push their QFs apart for driving bond activations for bond rearrangements. This is powerful as by this theory ^{1, 2, 3} introduces new types of interactions as two or more objects interact in counter ways on different states on L frames they attract but smaller frames they repel and/or on L frames they repel and on smaller RS frames they attract. Something on inside binds whole and whole repels. Or something on inside repels as whole binds! This is new by author for how particle ⟷ wave. This is new basis for compositie forces. The author published this in 2007 as p⁺ and nuclei bond e^- e^- of covalence by fissing of p⁺ and nuclei to create QFs to bind the e^- e^- pairs. So it is that the ¹⁷O can attack as it breaks up many + … + ... + ... + ... + NMMs. This may explain Ag nanoparticle atomizes due to the interactions of all its negative NMMs. So now this ³³S, ²D, and it ¹⁴N help pull in ¹³C and ¹⁷O as such lowers E_actfor such isotopic replacements inside organisms for replacements of primordial isotopes by nonprimordials. But what about ¹⁵N; it lowers E_act at higher temp but at lower temp it pushes ¹³C away.

The observed higher deuterations, methylations, aminations, hydroxylations and enrichments with ¹³CH₃¹⁵NH₂ and ¹⁷OH in cancer cells is consistent with nonrandom clustering and higher density methylations in DNA of cancer cells ¹⁰. Moreover, in this work in addition to explaining faster methylations by ¹³CH₃ to cause cancer, the faster methylations are explained in details by the accelerated ¹⁷OH hydroxylations and many body ¹⁵NH₂ aminations, causing the transformations of C →T → U and A → G for chemically altering DNA and RNA for new chemical paths of DNA and RNA mutations for explaining cancer. ¹³CH₃ may be causing more methylations of DNA in cancer cells as in this theory ^{1, 2, 3}, ¹³CH₃ is a stronger nucleophile than ¹²CH₃. This isotopic effects of the nucleic acids can explain recent mysteries. Positive NMMs of ¹³CH₃ relative to null (0) NMMs of ¹²CH₃ by the theory ^{1, 2, 3} cause the e^- e^- to be pulled closer to nucleus of ¹³CH₃ relative to ¹²CH₃ nuclei. ²⁴Mg²⁺ should interact less strongly with ¹³CH₃ (and make ¹³CH₃ a stronger nucleophile) relative to ²⁵Mg²⁺ for more altering the bonding of ¹³CH₃ by ²⁵Mg²⁺ in cancer cells relative to the weaker effect of ²⁵Mg²⁺ and/or ²⁴Mg²⁺ interacting with ¹²CH₃ in the normal cells to explain the observed selective killing of cancer cells by ²⁵Mg²⁺¹¹. This accumulated ¹³CH₃ in RNA and DNA then alters RNA and the RNA alters translated proteins for mechanism of splicing phenomena. ¹². This theory of RBL determines the chemically altered RNA by nonprimordial isotopes causes the splicing of proteins that is hallmark for cancer genesis and habitats. The transmuting of ¹²CH₃ to ¹³CH₃ of the space twin relative to the earth bound twin would explain the observed elongation of the telomeres of the space twin as by ¹³CH₃ methylations of his telomeres and stronger binding of his telomeres by ²⁵Mg²⁺ for elongation rather than shortening of the telomeres of space orbiting twin ¹³. The stronger binding of the telomeres containing ¹³CH₃ may less frazzle the ends for continued elongations.

So after reasoning and explaining how the nucleotides are isotopically mutated and some consequences, here it is considered how altered genes malfunction. So these alterations of nucleotides alter the sequencings, constitutions, connectivities and stereochemistry of isomers so what are consequences? Based on this model ^{1, 2, 3}, the methylations of the cytosine not only causes the cytosine not to bind guanosine, but moreover the methyl-cytosine may be misread as thymine and vice versa the thymine may be misread as methyl-cytosine. These are some of the consequences of changing the isotopes in nucleotides. The normal base pairs are GC and AT pairs. Also the functionalizations / defunctionalizations can alter the DNA and RNA sequencing transformation C → T→ U and A →G so as to alter DNA and RNA and alter proteins for changing RNA, DNA and proteins content in cells to damage cells. So C may be methylated similar to A and OH^- may replace NH₂^- for C → U. So methylation of C and deaminatation forms C and U for mutations and for consequent possible misreading of protein; so for example UUC (Phe) → UUU (Phe), CUU (Leu), CUC (Leu), CUA(Leu), and/or CUG (Leu) → UUU (Phe), UUC (Phe), UUA, UUG (Leu). So in some cases U and C can interchange without misreading protein, but in other cases such changes cause misreading and mutations. Likewise mutations as C → T and → G → A can cause splicing of proteins as by the change in translations of amino acids. Thereby chemically interchanges in nucleoside sequences change the selection of peptides to alter proteins. Stops in nucleic acids do not involve C: UAA, UAG, UGA! The creation of organisms may have intentional avoided C in stops as the mutations of C would affect stops. The G is in stops and mutations of G may cause stops in nucleic acids not to stop for a basis or cancer. Thereby DNA is altered by nonprimoridals substituting for primordials.

The ¹³CH₃ binding may alter interactions and dynamics due to its different NMMs. Although thymine already has a ¹²CH₃, by changing the ¹²CH₃ to ¹³CH₃, the properties of the thymine change so that the ¹³CH₃ may appear like H on the phenyl ring of thymine; so thymine appears to behave like uracil for altered replications, transcriptions and translations. Such ¹³CH₃ and its + NMM may appear as ¹H so the thymine in nucleus of cells appears like uracyl (U) with alterations of the DNA replications and transcriptions inside the nucleus. So it is that U can exist in the nucleus but thymine (T) exists only in the nucleus. But if ¹³CH₃ replaces ¹²CH₃ on thymine then thymine appearing as uranyl can exist in cytoplasma also to alter biochemistry in cytoplasma. And uranyl can methylate to enter nucleus. This means that uracyl in the nucleus can be template as thymine (as ¹³CH₃ in thymine causes it to appear as uracyl). Or the other possibility is that the ¹³CH₃ in thymine causes it to not be recognized. A third possibility is that the ¹³CH₃ causes the similar nuclear behavior as H so the thymine may behave as cytosine assuming the =O (OH) and NH₂ manifest similar basic interactions. So these are possible consequences of ¹³CH₃ on the thymine.

In addition to these nonprimordial, induced misreads of nucleic acids and proteins and nonprimordial, induced, inter-chemical transformations of C →T → U and G → A, this mechanism ^{1, 2, 3} further determines the consequent deficiency in C and G due to the + NMMs of ¹³CH₃ and – NMMs of ¹⁷O and ¹⁵N by difficult hydroxylations of A → G due to ¹⁷O and difficult demethylations of T → C. The consequent dynamics cause deficiencies in C and G ^{14, 15, 16, 17, 18} in cancer cells. The deficient C and G ^{14, 15, 16, 17, 18} on basis of this theory ^{1, 2, 3} causes deficient proteins translated by C and G ^{14, 15, 16, 17, 18}. See Figure 4. For instance, G and C strongly translate Gly (GGU, GGC, GGA, GGG) ²¹. {Note Gly and Pro are extremely important for alpha helical breakers. Gly and Pro start secondary structures of beta turns. Beta turns are turns in primary structure. Pro ¹⁹ has odd, cyclic structures in peptide bonds and these cause bendings of peptides. Gly has small size and can have large conformational changes due to lack of steric hindrance by Gly due to its small size. Bending breaks alpha helicies.}

Figure 4.Nucleotide Codons for Amino Acids (reference 9)

The Arg ²³, Try ²² and Ala ²⁰ also have strong translations by G and C and shortages of C and G in cancer cells are here reasoned to cause cancer habitat and transform normal cells to cancer cells: Arg* (CGU, CGC, CGA, CGG); Trp* (UGA, UGG), Pro (CCU, CCC, CCA, CCG); and Ala (GCU, GCC, GCA, GCG). ^{19, 20} Quite interesting, Arg and Trp are also essential amino acids; and this enforces this theory of the cancer genesis due to shortages of G and C and the inability to synthesize the Arg and Trp translated by G and C. But then other amino acids are marginally affected by deficient G and C: Leu (CUU, CUC, CUA, CUG); Val* (GUU, GUC, GUA, GUG); Ser (UCU, UCC, UCA, UCG); Thr (ACU, ACC, ACA, ACG); Asp (GAU, GAC); Glu (GAA, GAG); Cys (UGU, UGG); His (CAU, CAC); and Gln (CAA, CAG). * means the amino acids are essential amino acids. But then, the following amino acids are not strongly affected by shortages in G and C contents in cancer cells: Phen* (UUU, UCC); Ile* (AUU, AUC, AUA); Met* (AUG); Try (UAU, UAC); Asn (AAU, AAC); and Lys* (AAA, AAG). So on basis of such deficient G and C causing deficient templating of amino acids to form proteins the following consequences are reasoned. The predicted deficient Gly, Arg*, Trp*, Ala, and Pro correlates with recent analyses of microenvironment of tumors. Van der Heiden ²⁴ recently observed microenvironments of tumors are depleted in Trp*, Arg* and Cys. It is also important to note that Try* and Arg* are essential amino acids, as cells cannot synthesize these essential amino acids. But Gly and Glutamate where found by van der Heiden ¹⁸ to be abundant in cancer microenvironments. But Gly can be synthesized. And Glutamate is nonessential and can be synthesized so this observed abundance of Gly and Glu are consistent with this theory of cancer ^{1, 2, 3}. The stops are encoded by UAA and UAG, therefore excess A and may cause high densities of stops. The telomerase has its own RNA (3’ – CCCAAUCCC 5’) for translating teloemerase. So telomeres cannot elongate and this is habitual of cancer cells as 13CH3 methylates C on telomerase, then the C of telomere cannot help elongate the telomerase. It is important that the telomerase translation involves a lot of C and by this theory the deficient C may affect telomerase formation, length and stability for causing cancer as the lack of C causes lack of telomerase and the lack of elongating telomeres which is one hallmark of cancer.

After discovery of this new DNA, RNA and protein chemistry by Little Effect via NMMs of nonprimordials, this work considers plants oligomers and possibly such chemical interactions of plant oligomers with human oligomers. This work determined that just as the RNA, DNA and proteins can undergo intrinsic internal accelerated methylations, deaminations, aminations, hydroxylations and deuterations of nonprimordials relative to primordials; then also foods having similar oligomeric structures can also exchange primordials and nonprimordials via functionalizations and defunctionalizations between dietary oligomers and nucleotides in the host. But what happens to DNA as animal products are consumed? Plant products have less nonprimordial, ¹³C, ¹⁵N, ¹⁷O and ²D in their nucleus acids. But how does such low nonprimimordials compare to animal DNA? Animals tend to have in general greater amounts of ¹³C and ¹⁵N relative to plants. Scientists find link between plant telomere and human telomere so plants live longer as by their lower nonprimordials relative to animals and humans. The diet and metabolism of tree differs from animals and trees have less motion and less energy demands so trees do not break down ¹³C compounds and then construct ¹³C as much in their DNA for high nonprimordial contents as occurs in animals and humans; so tree DNA less mutates so trees live longer. The theory here determines that penalty of motion as by needed catabolic metabolism is breaking nonprimordial molecules and consequent uptake nonadiabatically of nonprimordials into DNA with mutations. Muscles and lysine cause ¹³C and cancer. Trees and plants use sunlight and operate adiabatically so less nonprimordials are taken up. Heat may help animals and plants pull in nonprimordials, plants operate cooler and pull in less nonprimordials. This explains how animals mutate DNA and develop cancer. This leads to cancer in humans and animals.

In this theory RBL tried to correlate cancer to motion and diet on this basis of nonadiabatic catabolism and uptake of nonprimordials by animals and humans. So eating cancerous DNA may also cause cancer to be transferred to host DNA and RNA. So cancer can be transferred by large transfer of cancerous tissues. Rats are implanted with cancer tissue with induction of cancer. In this work, it is reasoned that cancer cells of different types may kill each other. Injecting different types of cancer into a tumor may kill the tumor as the DNA and RNA of the two cancers differ. It may be possible to kill tumors and cut it out by surgery. The nonprimordials are determined to accelerate such new chemistry by differences in kinetic and thermodynamics of functionalizations and defunctionalizations. Thereby a new chemistry is described based on discovered for nucleotides based on NMMs and magnetics driving substitutions of NMMs and a mechanism ^{1, 2, 3} by which NMM substitutions can couple and mix with nucleophilic substitution energies. So by replacing new oligomers with nonzero NMMs in heavier isotope, the DNA of normal cells is disrupted to cause cancer. But in this work, it is further determined that just as the isotopic accumulations can transform normal cells to cancer cells, excessive nonprimordials can accumulate to kill cancer cells. Grape seeds may kill cancer but they may cause cancer as in this work, the grape seeds have oligomers of proanthocyanidins, which are in this work determined to have excess ¹³CH₃, ¹⁷OH, ¹⁵NH₂, and/ or ²D that can replace ¹H, ¹²CH₃, ¹⁴NH₂, and/or ¹⁶OH in cancer to oversaturate the cancer DNA with nonprimordials to kill the cancer.

It has already been published in 2007 ¹ that the + NMMs and nuclei of ¹⁴N, ¹⁶O and ¹²C via the proton (¹H) can magnetically couple for novel many-body nuclear magnetic moments (NMMs) and nuclear orbitals to cyclically move, transform and transmute for normal anabolism and catabolism. Thereby it is determined that without such effects of the protonic nuclei, life cannot exist and thereby disease may be caused by altering this natural rhythm ¹. For instance, consider intrinsically the ³¹PO₃ gives P center strong ability to attack ADP and AMP. So if change ¹²C to ¹³C then ¹³C makes ¹³CH₃ a stronger nucleophile; and if change ¹⁶OH to ¹⁷OH then ¹⁷OH is a weaker nucleophile and if change ¹⁴NH₂ to ¹⁵NH₂ then ¹⁵NH₂ a weaker nucleophile. So just as there is intrinsic NMM chemistry of ³¹PO₃ then there is new chemistry by NMMs in ¹³C, ¹⁵N and ¹⁷O; ¹³C attacks more than ¹²C; ¹⁷OH attacks less than ¹⁶O. ¹⁷OH attacks differently than ¹⁶OH attacks; so it is not that ¹⁷O does not attack, but ¹⁷O attacks differently than ¹⁶OH. ¹³CH₃ attacks more with ¹⁷OH than with ¹⁶OH. ¹⁷OH attacks ¹⁵NH more. It is that + NMMs attack + NMMs more in L Frame but less in L Continua and Nuclear Frames (NS Frames). {Where interior quarks are in QS Frames; quarks are inside hadrons in RS Frames; hadrons are inside nuclei in NS Frames.} The NS frames couple continuously to interior LS continua of the electronic lattice outside the nuclei. Electronic orbitals exist in L frames (discontinua); Electrons manifest continua about them for ES Frames and discontinua within the electron for E Frames. The ES frames of the electron can couple to the outer L continua of the electronic lattices to mix with the inner L continua of denser NS frame fields and such mixing of ES Frames and NF frames with diminution of stretch; transform and combine with other outer L Continua of other atoms, leptons and hadrons to manifest the C Frame (macroscopic frame) of magnetic fields, gravity, electric and thermal fields and spaces}. It is that + NMMs attack – NMMs less in L Frames and more in NS Frames. So thereby pressure effects manifest as high pressures push then the + NMMs into – NMMs; so the L Frames – NMMs repel + NMMs → NS Frames + NMMs attracting – NMMs at higher pressures.

This is consistent with RBL theory of high temperature superconductivity and why high pressures cause superconductivity. So now also with cancer as the cancer involves changing pressure the cancer may not metabolize as well; and by theory ^{1, 2, 3} this explains the changes in cancer as the host moves from surface of earth to outer space to kill the cancer due to changes in gravity and pressure. By this theory, the primordial isotopes of ¹H, ¹²C, ¹⁴N, ¹⁶O, ²⁴Mg and ³²S manifest in normal cells at earth surface and atmospheric pressure with all positive NMMs; so all positive NMMs attract in L frames. But as cancer forms by ²D, ¹³C, ¹⁵N, ¹⁷O, ²⁵Mg and ³³ S on the earth’s surface, then the nuclei have + and – NMMs and + and – NMM repel in L frames. But if the normal cells and cancer cells are accelerated into outer space then the lower pressure as gravity becomes zero and the lost gravity in outer space less pushes + … + NMMs of normal cells to NS Frames for repulsion, so normal cells are less affected by earth’s gravity (this can also be a basis for new magnetic sensing of earth’s magnetic field by normal cells.) So now cancer cells on the other hand, have + and – NMMs and the loss pressure increases there + and – repulsions in L Frames to alter biochemical dynamics more in cancer relative to normal cells and may cause the cancer tissue to bind on larger scales for possibly killing the cancer. But such altered L Frames alter the glycolysis to kill cancer due to zero gravity. It is that ¹⁷O helps ¹³C in C Frame magnetically, but then ¹⁷O pushes ¹³C away in L Frames’ QFs. But then under compression ¹⁷O pulls ¹³C to it in inner L Continua and in NS Frames. This is how the ¹³C and ¹⁷O interact differently in complex ways on different scales to cause accelerated mutual replacements and substitutions for ¹⁶O and ¹²C in living organisms.

So the interactions are contravariant on different scales as attract on nuclear scale (NS Frame) and repel on QF scale (L Frames) and attract on magnetic frame of C Frame. It is that as something pulls another to it, but simultaneously can push it away simultaneously. Thereby this is new dynamics that by the theory ^{1, 2, 3} explains transformations of it and transmutations of it for new mechanics as introduced here by RBL. And this is how transport goes to transform and to transmute and vice versa. As transport is by push but if push so hard then it pulls as it pushes to stretch and pull it towards to transform it and to transmute it as by this theory of RBL! So ¹⁷O transmutes ¹³C where as ¹⁴N NMM pushes ¹³C away. ¹⁷O pulls ¹³C to its nucleus and pulls ¹³C atomic orbitals apart and magnetically binds ¹³C as it stretches its orbitals! This is a new type physics of chemistry as by nuclear magnetic moments (NMMs) and nuclear spins under very high temperatures, strong electric fields and strong magnetic fields ^{1, 2, 3}. Simultaneous nuclear, chemical, and physical transformational phenomena are determined by the theory ^{1, 2, 3} to occur! So it is as the ¹⁷O internally binds it; it also stretches it and holds it globally! But ¹⁴N internally pushes ¹³C away as it binds it in QF and magnetically globally repels it!

So after considering/discussing the peaks and the nucleosides and how cancer DNA therefore has different peaks relative to DNA of normal cells and the different peaks are due to nonprimordials, next oligomeric in grape seeds ²⁵ and the seeds are considered and compared to these nucleotides in normal and cancer cells. The novel chemical alterations of DNA and RNA by grape seeds oligomers are considered. The grape seeds are the cellular nucleic of the fruits with reproductive ability. So the biochemistry and biomolecules of grape seeds reproduction couple to biomolecules of human reproductions and malignant reproductions as by cancer so thereby the grape seed may couple to cell to cause cancer and/or to kill the cancer. The plants are observed to accumulate ²D, ¹³C, ¹⁵N and ¹⁷O in their proanthocyanidins in grapes with water deficit having more ¹⁷O and the ¹⁷O pulls in more ¹³C into seed ²⁶. This is in the literature ²⁶. It has been observed that the draught and ¹³C and ¹⁷O in the seeds make the seeds more anti-cancerous ²⁵. What is it about grapes that they incorporate ¹³C and ¹⁷O among the plant kingdom? In this theory, it is determined that the chemistry of ¹³C, ¹⁸O and ¹⁷O cause greater incorporation of nonprimoridals in grape seed proanthocyanidins as by aromatic background network of the oligomers. The corn may have similar background oligomers to help it pull in more ¹³C in C4 process relative to C3 process ²⁷.

In consistency of this reasoned aromatic, alkyl background network accelerating nonprimordial uptake by coupling NMMs as by this theory, researchers recently report larger plant oligomers have greater anticancer effects ^{7, 8, 15}. The larger proanthocyanidins are more anticancerous as they have more nonprimordials isotopes and they pull in more nonprimordials; release more nonprimordials by extended C-C bonds and π bonds and/or bind nonprimordial isotopes existing in DNA, RNA and proteins and causing cancer and other diseases. Also consider that the enzymes of Kreb cycle may be able to pull in more nonprimordials relative to enzymes of glycolysis due to the high field substrates of Kreb cycle. Both such networks of changing covalence in Kreb cycle and changing covalence of glycolysis process and the oligomerics of proanthocyanidins manifest changing covalence in extended arrays of sp² and sp³ covalence with intrinsic magnetics of the changing covalence and with embedded p⁺ and NMMs of other nuclei. By such Ferrochemistry the nuclei revolve to orbitals as by fractionally fissing their NMMs so as to couple the covalence and to alter the many covalence for breaking covalence by the many NMMs and pulling in nuclei and pushing out nuclei and rebonding covalence to new nuclei. Such explains the isotopic replacements by the covalent lattices with embedded NMMs in accelerated many-bodies relative to null NMMs as by the theory^{1, 2, 3}. It is noticed that the greater enrichments of nonprimordial isotopes in the heavier isotopes correlate to the anti-cancer.

On this basis, a new idea ^{1, 2, 3} is presented. It may be that the different ferrochemistry of glycolysis, Kreb, replication, transcription, and translation can be reasoned by functional groups of amino acids as the alkyl + phenyl functionals may in proteins push together to induce greater nonprimordial uptakes. Also the ¹⁷OH and ¹⁵NH regions of functionals in proteins more push together to lower E_act for such ¹³C substitutions or to accelerate incorporations of ¹⁷O and ¹⁵N. So if the theory ^{1, 2, 3} looks at enzymes of glycolysis, it may find fewer Leu and Trp than in Kreb cycle. Kreb cycle may have more Trp and Leu so it would more incorporate ¹³C relative to glycolysis.

Proanthocyanidins are observed in grape seeds, cranberries and other fruits and vegetables ¹³. The greater amounts of proanthocyanidins (PACs) in grape seeds and cranberries are revealed in mass spectrometer as isotopic clusters are observed in Figure 5. The nature of the interflavan bonds (D2 amu) [M+Na}⁺ represented by observed masses. The PACs from grape seeds contain B type (m/z 1465) bonds. Masses represent variations in the nature of interflavan bonds (D2 amu) ^{M + Na+}. It is noticed that from the mass analyses, that the grape seeds explicitly show huge enrichments of either ²D, ¹³C, ¹⁵N and/or ¹⁷O in the mass spectra, but the authors of these prior data ¹³ do not correlate such properties of isotopes in the proanthocyanidins (PACs) to anti-cancer. Isotopes of predicted compounds are observed in the spectra with characteristic masses (m/z). For instance, the predicted monoisotopes for PAC of 5 DP with 4 B type interflavan bands are observed at 1465 m/z, which are observed to have primordials of ¹²C, ¹⁴N and ¹H. See Figure 6- Figure 7. But mass of 1466 m/z is observed of similar intensity as the 1465 m/z for similar relative concentrations so that the 1466 m/z has possible contributions from possibly one ¹³C, one ²H or one ¹⁷O. The mass at 1467 m/z may have two of these nonprimordials ²D, two ¹³C or two ¹⁷O. The similar intensities of 1465, 1466 and 1467 m/z determine similar relative abundances and thereby isotopic enrichment of nonprimordials in the PACs. But in this work, the anticancer activity of proanthocyanidins is correlated with there enrichments with nonprimordial isotopes of ²H, ¹³C, ¹⁵N, ¹⁷O. Furthermore, the proanthocyanidins may be anti-cancer as by the similar chemical structures of the tannins and polyphenols to the nucleosides and the possible exchange of the nonprimordial isotopes between the nucleosides of RNA and DNA; and possibly more favorable binding of the nonprimordial enriched proanthocyanidins with nonprimordial enriched DNA and RNA in cancer cells. The proanthocyanidins may also alter the translations of proteins in cytoplasma and the synthesis of DNA in nucleus. In this work, it is determined that the nonprimordial isotopes couple (bind) more strongly to the cancer DNA and RNA relative to the RNA and DNA of normal cells, because by this theory ^{1, 2, 3} and data, the cancer DNA and RNA are isotopically different from the normal cells RNA and DNA. The stronger binding of tannin to cancer DNA is due to similar clumping of nonprimordials. The nonprimordials in grape oligomers may also chemically alter the DNA in cancer so as to alter cancer’s replication. Thereby the grape seeds provide the epigenetics to alter cancer DNA selectively so the seeds are anti-cancerous and this is the first molecular basis for anticancer properties of grape seeds. This is consistent with prior theory ^{1, 2, 3} for also treating cancer by the prior theory ^{1, 2, 3} as by the prior theory, it was proposed to use of nonprimordial enriched foods to selectively target the cancer. So the prior theory ^{1, 2, 3} looks at the DNA in the human and the cancer and finds the nonprimordials, and the prior researchers find nonprimordials in the seeds of grapes. So in this work, the nonprimordials in cancer and in grapes are correlated for anticancer activity of grape seeds. And the grape nonprimordials disrupt the cancer nonprimordials.

Figure 5.Oligomeric Proanthocyanidins from Adzuki Beans With Those Larger than Tetramers Showing AntiCancer Activities (reference 8)

Figure 6.Grape Seed Proanthocyanidins (PAC) Isotopic Reveal Isotopic Enrichments (reference 14)

Figure 7.Structures and Masses of Nonprimordial Isotopes in Plant Proanthocyanindins (Reference 7)