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 mechanism of action is not well understood. It has been proposed that BLM cytotoxicity is mediated through the generation of reactive oxygen species. We have determined the effects of BLM on endogenous hepatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase, and glucose-6-phosphate dehydrogenase in rats exposed to BLM in conjunction with dietary vitamins, vitamin C and beta-carotene (BC). Male Fischer 344 rats of two different age groups were treated with BLM in 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 vitamin C was significant (p < 0.05) compared with BLM-treated young animals fed vitamin C. BC moderately induced GPx and glutathione reductase activities in old BLM-treated animals; however, the increase in GPx was statistically significant (p < 0.05) only compared with old controls. A similar increase was noted in the activities of all the enzymes examined in young animals. Our results indicate that BLM exposure was accompanied by alterations in the activities of endogenous antioxidant enzymes, with a profound increase in activities occurring in old animals. In addition, the observed enzyme activities were modulated by antioxidant vitamin administration. The observation that both vitamins displayed differential effects on the enzyme activities also suggests that vitamin C and BC exert their effects by separate mechanisms.
Desai
V G
VG
Division of Genetic Toxicology, National Center for Toxicological Research, Food and Drug Administration, US Department of Health and Human Services, Jefferson, AR 72079, USA.
Lyn-Cook
L E
LE
Aidoo
A
A
Casciano
D A
DA
Feuers
R J
RJ
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D015331:Cohort Studies; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D019207:beta Carotene; D001761:Bleomycin; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D001205:Ascorbic Acid