The metabolism and activation of 15,16-dihydrocyclopenta[a]phenanthren-17-one by cytochrome P-450 proteins.
The in vitro metabolism and activation to mutagens of 15,16-dihydrocyclopenta[a]phenanthren-17-one (CPP-17-one) were investigated using hepatic preparations from rats pretreated with prototype inducers of the cytochrome P-450-dependent mixed-function oxidases. Aroclor 1254-induced microsomes were the most effective metabolisers of this compound, the major metabolites being oxidation products of the bay region A ring. To a lesser extent hydroxylation of the non-aromatic D ring occurred, the products being the 15- and 16-hydroxyderivatives. Oxidation of the A ring was also achieved with microsomes from benzo[a]pyrene-treated rats but not with those from rats treated with clofibrate, phenobarbitone, isoniazid, dexamethasone and CPP-17-one itself, where the metabolites were primarily the oxidation products of the D ring. When CPP-17-one was used as a promutagen in the Ames test, only microsomes from Aroclor 1254-treated rats could elicit a positive mutagenic response. When 3,4-dihydrodihydroxy-CPP-17-one, the precursor of the ultimate mutagen, was used as the promutagen, a positive response was observed with microsomes from Aroclor 1254- and benzo[a]pyrene-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Boyd
G W
GW
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
Young
R J
RJ
Harvey
R G
RG
Coombs
M M
MM
Ioannides
C
C
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006067:Gonanes / Q000378:metabolism* / Q000633:toxicity; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D051381:Rats; D017208:Rats, Wistar
D001140:Aroclors; D002273:Carcinogens; D006067:Gonanes; D020111:Chlorodiphenyl (54% Chlorine); C011770:15,16-dihydrocyclopenta(a)phenanthren-17-one; D003577:Cytochrome P-450 Enzyme System