Catterall F S, Coombs M M, Ioannides C, Walton K
Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Mutat Res. 2000 Feb 16;465(1-2):85-90. doi: 10.1016/s1383-5718(99)00215-6.
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.
