MAGNESIUM INHIBITS NICKEL-INDUCED GENOTOXICITY AND FORMATION OF REACTIVE OXYGEN

Nickel compounds are recognized to cause nasal and lung cancers. Magne sium is an effective protector against nickel-induced carcinogenesis i n vivo, although its mechanisms of protection remain elusive. The effe cts of magnesium carbonate on the cytotoxicity and genotoxicity induce d by nickel subsulfide were examined with respect to the inhibition of cell proliferation, micronuclei formation, DNA-protein cross-link for mation, and intranuclear nickel concentration. The generation of react ive oxygen by nickel chloride was also analyzed by observing 8-hydroxy -deoxguanosine formation from deoxyguanosine in the presence and absen ce of magnesium chloride. The suppression of up to 64% of the prolifer ation of BALB/3T3 fibroblasts by nickel subsulfide (1 mu g/ml) was rev ersed by magnesium. The nickel compound increased not only the number of micronuclei but also the amount of DNA-protein cross-links examined with CHO and BALB/3T3 cells, respectively. These genotoxic effects of nickel were again lessened by magnesium carbonate. In addition, the c ellular accumulation of nickel increased 80-fold with nickel subsulfid e treatment and decreased with magnesium carbonate treatment. Nickel a lso enhanced 8-hydroxy-deoxyguanosine formation in the presence of H2O 2 and ascorbic acid, where magnesium played another suppressive role. In fact, inhibition by magnesium was still observed even in the absenc e of nickel treatment These results suggest that the protective role o f magnesium in nickel-induced cytotoxicity and genotoxicity can be att ributed to its ability to reduce either the intracellular nickel conce ntration Or reactive oxygen formation.