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

• Published in: Carcinogenesis (New York) Vol. 14; no. 8; p. 1697
• Main Authors: Boyd, G W, Zepik, H H, King, L M, Ioannides, C, Coombs, M M
• Format: Journal Article
• Language: English
• Published: England 01.08.1993
• Subjects: Animals; Biotransformation; Carcinogens - pharmacokinetics; Carcinogens - toxicity; Gonanes - pharmacokinetics; Gonanes - toxicity; Mass Spectrometry; Microsomes, Liver - metabolism; Mutagenicity Tests; Mutagens - pharmacokinetics; Mutagens - toxicity; Rats; Spectrophotometry, Ultraviolet
• ISSN: 0143-3334
• DOI: 10.1093/carcin/14.8.1697

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.