TY - JOUR
T1 - The in vitro metabolic activation of the 11-trifluoromethyl analogue of the potent carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to mutagens
AU - Boyd, Gary
AU - Zepik, Helmut H
AU - King, Lloyd M
AU - Ioannides, Costas
AU - Coombs, Maurice M
PY - 1993/8
Y1 - 1993/8
N2 - 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.
AB - 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.
U2 - 10.1093/carcin/14.8.1697
DO - 10.1093/carcin/14.8.1697
M3 - Article
SN - 1460-2180
VL - 14
SP - 1697
EP - 1699
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -