A comparative examination of the in vitro metabolism of five cyclopenta[a]phenanthrenes of varying carcinogenic potential

Metabolites of 15,16-dihydrocyclopenta[a]phenanthren-17-oneand its 1- and 12-methyl homologues (all non-carcinogens) alongwith those from the 11-methyl and 11, 12-dimethyl-17-ketones(carcinogens), produced in vitro by hepatic microsomes frommethylcholanthrene induced rats, were separated by reverse phaseh.p.l.c. Identifications of individual metabolites were basedupon elution times, u.v. spectra, and in some cases by massspectrometry, circular dichroism, and identity with syntheticderivatives. All five compounds were biologically oxidised attheir terminal A and D rings to yield 1,2-dihydrodiols and 15-and 16- ols; with the exception of the 1-methyl compound, allalso gave similar amounts of 3, 4-dihydrodiols. The 1-methylcompound by contrast failed to produce this metabolite, furnishinginstead the 4-phenol and five other, probably related phenolicderivatives. Previous work has established that for the 11-methyl-17-ketone,the 3, 4-dihydrodiol is the proximate carcinogen. Thus, whereaslack of biological activity with the 1-methyl compound can beascribed to its failure to produce a 3,4-dihydrodiol, in thecase of the unsubstituted parent ketone and its 12-methyl derivativeother determining factors must come into play.