Inhibition of cyclophosphamide mutagenicity by beta-carotene.
Cyclophosphamide (CP) metabolites, rather than the parent compound, show mutagenic activity towards Salmonella typhimurium TA 1535 tester strain when S9 fraction from phenobarbital (PB)-induced rat liver is used as in vitro metabolizing system. On the other hand, inhibition of CP in vitro mutagenicity was observed by adding increasing amounts of beta-carotene (beta-C) to the system. A typical dose-dependent mutagenic response was observed by assaying 24 h urine samples of PB-induced rats injected i.p. with different amounts of CP. Addition of beta-C to urines of CP-treated rats failed to inhibit their mutagenicity. Conversely, a marked decrease in urine mutagenicity was observed when rats were simultaneously treated with the two drugs. These data show that beta-carotene partially inhibits, in vitro and in vivo, CP metabolism via hepatic mixed-function oxidase enzymes to mutagenic species.
D000818:Animals; D001711:Biotransformation; D002338:Carotenoids / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity / Q000652:urine; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D019207:beta Carotene
D019207:beta Carotene; D002338:Carotenoids; D003520:Cyclophosphamide; D010634:Phenobarbital