Modulation of genotoxic activity of tobacco smoke

Tobacco smoke (TS) caused a three- to nine-fold increase in the frequency of his+ revertants in Salmonella typhimurium TA98 but not in TA97a, TA100 or TA102. Activation by a post-mitochondrial fraction obtained from the liver of rats pretreated with Aroclor-1254 or methylcholanthrene was required; fractions from phenobarbital-pretreated or untreated rats had no effect. Vitamins A and E, but not ascorbic acid, inhibited the TS-induced mutagenesis by up to 63%, whereas glutathione and cysteine increased it slightly. Na2SeO3, but neither CoCl2 nor caffeine, inhibited the mutagenic effect of TS by 46-56%. In Chinese hamster ovary cells, both Na2SeO3 and caffeine strongly potentiated the number of chromosomal aberrations induced by TS, while theophilline slightly reduced its clastogenic effect. Treatment of mice with TS for 60 min/day increased the frequency of micronuclei in polychromatic erythrocytes in bone marrow and in fetal liver and the number of NCE micronuclei in peripheral blood by four to five fold. Simultaneous treatment of mice with TS and Na2SeO3 reduced the clastogenic effect of TS. Ascorbic acid had no effect on clastogenicity but reduced toxicity as measured by body weight loss. Both Na2SeO3 and ascorbic acid suppressed the induction of TS-induced hyperplastic and metaplastic changes in bronchial mucosa but had no effect on the number of urethane-induced lung adenomas. Vitamins A and E and ascorbic acid may have a protective effect against the toxic and genotoxic activities of TS.