MODULATION OF ANTIOXIDANT ENZYMES IN BLEOMYCIN-TREATED RATS BY VITAMIN-C AND BETA-CAROTENE

Bleomycin (BLM), an antineoplastic drug, is known to induce DNA strand breaks and is also mutagenic in mammalian cells, however, its mechani sm of action is not well understood. It has been proposed that BLM cyt otoxicity is mediated through the generation of reactive oxygen specie s. We have determined the effects of BLM on endogenous hepatic antioxi dant enzymes such as glutathione peroxidase (GPx), glutathione reducta se, and glucose-6-phosphate dehydrogenase in rats exposed to BLM in co njunction with dietary vitamins, vitamin C and beta-carotene (BC). Mal e Fischer 344 rats of two different age groups were treated with BLM i n the presence or absence of antioxidant vitamins. In control animals, an age-associated decrease in GPx activity was noted (p < 0.05). The decrease in GPx activity observed in BLM-treated old animals given vit amin C was significant (p < 0.05) compared with BLM-treated young anim als fed vitamin C. BC moderately induced GPx and glutathione reductase activities in old BLM-treated animals; however the increase in GPx wa s statistically significant (p < 0.05) only compared with old controls . A similar increase was noted in the activities of all the enzymes ex amined in young animals. Our results indicate that BLM exposure was ac companied by alterations in the activities of endogenous antioxidant e nzymes, with a profound increase in activities occurring in old animal s. In addition, the observed enzyme activities were modulated by antio xidant vitamin administration. The observation that both vitamins disp layed differential effects on the enzyme activities also suggests that vitamin C and BC exert their effects by separate mechanisms.