title: The in vitro metabolic activation of the 11-trifluoromethyl analogue of the potent carcinogen 15,16-dihydro-11-methyl-cyclopenta[a]-phenanthren-17-one to mutagens.
abstract: A strongly electronegative, bay-region analogue of the potent carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one, namely 15,16-dihydro-11-trifluoromethylcyclopenta[a]phenanthren-17-one, is mutagenic to Salmonella typhimurium TA100. Also it is metabolized at the 1,2- and 3,4-positions in the A-ring as well as C-15 in the D-ring to give 3,4-dihydroxy-3,4,15,16-tetrahydro-11-trifluoromethyl- cyclopenta[a]phenanthren-17-one as the only mutagenic metabolite. In these respects its behaviour is closely similar to that of the 11-methyl compound, suggesting that the electronic nature of the bay-region substituent is rather less critical than its spatial configuration in influencing metabolism to genotoxic intermediates. It remains to be seen, however, whether the trifluoromethyl compound is also a carcinogen.
authors.affiliation: School of Biological Sciences, University of Surrey, Guildford, UK.
authors.forename: G W
authors.initials: GW
authors.lastname: Boyd
authors.forename: H H
authors.initials: HH
authors.lastname: Zepik
authors.forename: L M
authors.initials: LM
authors.lastname: King
authors.forename: C
authors.initials: C
authors.lastname: Ioannides
authors.forename: M M
authors.initials: MM
authors.lastname: Coombs
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D006067:Gonanes / Q000493:pharmacokinetics* / Q000633:toxicity; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002273:Carcinogens; D006067:Gonanes; D009153:Mutagens; C005765:15,16-dihydro-11-methylcyclopenta(a)phenanthren-17-one