T. Wronskanofer et al., GENOTOXICITY OF CADMIUM AND NICKEL AS DEPENDENT ON ETHANOL-INDUCED CYTOCHROME-P-450 - ROLE OF FREE-RADICAL MECHANISM, Trace elements in medicine, 14(2), 1997, pp. 96-101
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.