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 from 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 derived from attack at the 5-membered ring, but no evidence of aromatic oxidation is apparent. The title compound is a weak mutagen in the Ames' test with Salmonella typhimurium TA100, but only with microsomal bio-activation. The 17-ol and 16,17-diol are inactive, with or without biological activation. By contrast the 15-alcohol, a rather reactive compound, is a strong mutagen both in the presence and absence of the bio-activation system. This, therefore, may be the proximate carcinogen, and its structural analogy to the naturally occurring hepato-carcinogen safrole is noted.
Catterall
F S
FS
Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Coombs
M M
MM
Ioannides
C
C
Walton
K
K
D000736:Androstenes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D000736:Androstenes; D002273:Carcinogens; C057010:16,17-dihydro-11-methoxy-15H-cyclopenta(a)phenanthrene