THE IN-VITRO METABOLIC-ACTIVATION OF THE 11-TRIFLUOROMETHYL ANALOG OF THE POTENT CARCINOGEN 15,16-DIHYDRO-11-METHYL-CYCLOPENTA[A]-PHENANTHREN-17-ONE TO MUTAGENS

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]phenanthre n-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.