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

摘要: Metabolites of 15,16-dihydrocyclopenta[a]phenanthren-17-one and its 1- 12-methyl homologues (all non-carcinogens) along with those from the 11-methyl 11,12-dimethyl-17-ketones (carcinogens), produced in vitro by hepatic microsomes methylcholanthrene induced rats, were separated reverse phase h.p.l.c. Identifications individual metabolites based upon elution times, u.v. spectra, some cases mass spectrometry, circular dichroism, identity synthetic derivatives. All five compounds biologically oxidised at their terminal A D rings to yield 1,2-dihydrodiols 15- 16- ols; exception 1-methyl compound, all also gave similar amounts 3,4-dihydrodiols. The compound contrast failed produce this metabolite, furnishing instead 4-phenol other, probably related phenolic Previous work has established that for 11-methyl-17-ketone, 3,4-dihydrodiol is proximate carcinogen. Thus, whereas lack biological activity can be ascribed failure a 3,4-dihydrodiol, case unsubstituted parent ketone derivative other determining factors must come into play.