GENOTOXICITY OF CADMIUM AND NICKEL AS DEPENDENT ON ETHANOL-INDUCED CYTOCHROME-P-450 - ROLE OF FREE-RADICAL MECHANISM

Genotoxic effect of cadmium (II) and nickel (II) salts of transition m etal group were evaluated in Balb C mice fed for 6 days alcoholic Liqu id diet containing 5% (w/v) ethanol (36% of total calories) or nutriti onally adequate liquid diet (1 kcal/ml) as a reference. The metal salt s were given intraperitoneally, 24 h before testing as follows: CdCl2 x 2.5 H2O at dose 2 mg similar to 18 mu mol Cd/kg and NiCl2 x 6 H2O at dose 12 mg similar to 200 mu mol Ni/kg body weight. Liver oxidant sta tus was assessed on a basis of determination of cytochrome P-450 (etha nol-inducible CYP2E1 form) and activity of associated monooxygenases, lipid peroxidation rate, and antioxidative potential of constitutive, primary free radical scavengers, glutathione peroxidase, and glutathio ne as well as inducible, secondary antioxidant, heme oxygenase. Bone m arrow micronucleus test was used for evaluation of genotoxic effect. C admium (II) and nickel (II) single treatment resulted in destruction o f cytochrome P-450 with induction of heme oxygenase, stimulation of li pid peroxidation, and a decrease of glutathione peroxidase in the live r. Ethanol-mediated induction of cytochrome P-450 and stimulation of l ipid peroxidation did not enhance the prooxidative effect of cadmium ( II) and nickel (II) superimposed on ethanol pretreatment. Cadmium (I) and nickel (II) increased frequency of micronucleated polychromatic er ythrocytes in bane marrow and ethanol did enhance that nickel (II)-med iated genotoxic effect although failed to potentiate the accompanying prooxidative processes. Genotoxic effect of cadmium (II) and nickel (I I) may be related at least in part to oxidant status derangement.