Magnetic isotope and magnetic field effects on the DNA synthesis

Abstract

Magnetic isotope and magnetic field effects on the rate of DNA synthesis catalysed by polymerases β with isotopic ions 24Mg2+, 25Mg2+ and 26Mg2+ in the catalytic sites were detected. No difference in enzymatic activity was found between polymerases β carrying 24Mg2+ and 26Mg2+ ions with spinless, non-magnetic nuclei 24Mg and 26Mg. However, 25Mg2+ ions with magnetic nucleus 25Mg were shown to suppress enzymatic activity by two to three times with respect to the enzymatic activity of polymerases β with 24Mg2+ and 26Mg2+ ions. Such an isotopic dependence directly indicates that in the DNA synthesis magnetic mass-independent isotope effect functions. Similar effect is exhibited by polymerases β with Zn2+ ions carrying magnetic 67Zn and non-magnetic 64Zn nuclei, respectively. A new, ion–radical mechanism of the DNA synthesis is suggested to explain these effects. Magnetic field dependence of the magnesium-catalysed DNA synthesis is in a perfect agreement with the proposed ion–radical mechanism. It is pointed out that the magnetic isotope and magnetic field effects may be used for medicinal purposes (trans-cranial magnetic treatment of cognitive deceases, cell proliferation, control of the cancer cells, etc).

Retinoblastoma: Magnetic Isotope Effects Might Make a Difference in the Current Anti-Cancer Research Strategy

“…Conventionally, the nuclear spin possessing metal isotopes were labeled as "magnetic" ones in numerous MIE-devoted biochemical reports (2,(10)(11)(12)(13)(14). In particular, mechanisms and pharmacological potential of MIE promoted by 25 Mg 2+ , 43 Ca 2+ and 67 Zn 2+ in DNApolβ reaction were in a focus of studies on human myeloblast leukemia cells (15,16). So far, however, this type of tumors was the only malignant objects studied with respect to MIE-DNApolβ impacts.…”

“…A trend making MIE-focused approach to ongoing anti-retinoblastoma clinical and pre-clinical efforts is about to rise now due to a revealed possibility of taking DNApolβ molecular machinery as a tumor specific target for the controlled ↓3.0 ↓2.4 * MIE value expressed as the specific catalytic activity of DNApolβ measured in the presence of pure "magnetic", nuclear spin possessing, metal ions corrected to its activity in the presence of the same content of ions of the same element abundant spinless isotopes [11,15,16].…”

Retinoblastoma Case: Shall we Get A Paramagnetic Trend in Chemotherapy?

“…In this case, a mode of the isotope anti-tumor action, caused by deprivation of the AML-specific DNA repair capabilities, has unambiguously determined by a number of circumstances including an MIE-allowing structural uniqueness of the DNA Polymerase Beta [4,5], hyperexpression of this target enzyme in AML [4] and by the ion-radical manner of the 25Mg 2+ -induced dysfunction of the tartget [2][3][4][5]. Considering the routine magnesium pharmacology profile, there is nothing obscure about the resulted Magnesium-25 safety profile too.…”

“…This itself is about to deprive the cell of its usual DNA repair capabilities [1,2,8] which is a reason to expect the tumor growth to get limited [3,9]. Thus, the MIE-dependent formation of these "size The applied medicinal significance of these data looks promising due to the followings: (a) the MIE ion-radical mode [4][5][6][7] does not allow the most members of DNA Polymerases diversity (α, γ, δ) to get operated this way since the electron transfer distances in their catalytic sites are too long to make a "magnet" manifesting its MIE [1,3,5]; while (b) DNApolB is a perfect target for MIE-ions considering this enzyme active site 3D-structure [4,7]. Besides, (c) the above specified "magnets" were proven of being the substantial subjects for a cancer targeted delivery conducted with the low-toxic amphiphilic nanocationites [5,11].…”

“…This also makes them legitimate targets for pharmacologically promising inhibitors [3] including paramagnetic (magnetic, in brief) bivalent metal ions, (nMe 2+ ) [4,5]. Being capable to promote the magnetic isotope effects (MIE) in vivo and in vitro these ions could be employed to "turn off" DNApolB to limit the tumor growth [6,7].…”