Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals.
Magnesium deficiency causes renal complications. The appearance of several diseases is related to its depletion in the human body. In radiotherapy, as well as in chemotherapy, especially in treatment of cancers with cis-platinum, hypomagnesaemia is observed. The site effects of chemotherapy that are due to hypomagnesaemia are decreased using Mg supplements. The role of magnesium in DNA stabilization is concentration dependent. At high concentrations there is an accumulation of Mg binding, which induces conformational changes leading to Z-DNA, while at low concentration there is deficiency and destabilization of DNA. The biological and clinical consequences of abnormal concentrations are DNA cleavage leading to diseases and cancer. Carcinogenesis and cell growth are also magnesium-ion concentration dependent. Several reports point out that the interaction of magnesium in the presence of other metal ions showed that there is synergism with Li and Mn, but there is magnesium antagonism in DNA binding with the essential metal ions in the order: Zn>Mg>Ca. In the case of toxic metals such as Cd, Ga and Ni there is also antagonism for DNA binding. It was found from radiolysis of deaerated aqueous solutions of the nucleoside 5'-guanosine monophosphate (5'-GMP) in the presence as well as in the absence of magnesium ions that, although the addition of hydroxyl radicals (*OH) has been increased by 2-fold, the opening of the imidazole ring of the guanine base was prevented. This effect was due to the binding of Mg2+ ions to N7 site of the molecule by stabilizing the five-member ring imitating cis-platinum. It was also observed using Fourier Transform Infrared spectroscopy, Raman spectroscopy and Fast Atom Bombardment mass spectrometry that *OH radicals subtract H atoms from the C1', C4' and C5' sites of the nucleotide. Irradiation of 5'-GMP in the presence of oxygen (2.5 x 10(-4) M) shows that magnesium is released from the complex. There is spectroscopic evidence that superoxide anions (O2-*) react with magnesium ions leading to magnesium release from the complex. From radiolysis data it was suggested that magnesium ions can act as radiosensitizers in the absence of oxygen, while in the presence of oxygen they act as protectors and stabilizers of DNA.
Anastassopoulou
J
J
National Technical University of Athens, Chemical Engineering Department, Radiation Chemistry and Biospectroscopy, Zografou Campus, Zografou 15780, Athens, Greece. ianastas@central.ntua.gr
Theophanides
T
T
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D006147:Guanine / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000528:radiation effects; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D017665:Hydroxyl Radical; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D008274:Magnesium / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D008275:Magnesium Deficiency / Q000150:complications; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009690:Nucleic Acid Conformation / Q000187:drug effects; D018384:Oxidative Stress; D011832:Radiation Injuries / Q000517:prevention & control; D011836:Radiation Tolerance / Q000187:drug effects; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014916:Whole-Body Irradiation / Q000009:adverse effects
D002413:Cations, Divalent; D013481:Superoxides; D017665:Hydroxyl Radical; D006147:Guanine; D006157:Guanosine Monophosphate; D004247:DNA; D008274:Magnesium