Bioactivation of the carcinogen 11-methoxy-16,17-dihydro-15H-cyclopenta[a]phenanthrene

The title compound is a more potent carcinogen than would be anticipated fr om its simple phenanthrene structure lacking further D-ring conjugation. In vitro it undergoes microsomal metabolism to yield as major metabolites its 15- and 17-alcohols and its 16,17-diol; other minor metabolites are also d erived from attack at the 5-membered ring, but no evidence of aromatic oxid ation is apparent. The title compound is a weak mutagen in the Ames' test w ith Salmonella typhimurium TA100, bur only with microsomal bio-activation. The 17-ol and 16,17-diol are inactive, with or without biological activatio n. By contrast the 15-alcohol, a rather reactive compound, is a strong muta gen both in the presence and absence of the bio-activation system. This, th erefore, may be the proximate carcinogen, and its structural analogy to the naturally occurring hepato-carcinogen safrole is noted. (C) 2000 Elsevier Science B.V. All rights reserved.