The biological activity and activation of 15,16-dihydro-1,11-methanocyclopenta[a]phenanthren-17-one, a carcinogen with an obstructed bay region.
The proposal that an unobstructed bay region is a prerequisite for tumorigenic activity in cyclopenta[a]phenanthrene-17-ones is not supported by the observation of the tumorigenicity of 15,16-dihydro-1,11-methanocyclopenta[a]phenanthrene-17-one towards the skin of T.O. mice. The title compound is oxidised in vitro by a mixed function oxidase to produce, inter alia, a trans-3,4-dihydrodiol, postulated as the proximate tumorigen. Unequivocal identification of a second metabolite as a trans-1,2-dihydrodiol derivative demonstrates the potential for enzymatic oxidation within the obstructed bay region and supports the proposal that the ultimate tumorigen is a trans-3,4-dihydrodiol-anti-1,2-oxide. This is further substantiated by the chromatographic behaviour of the major hydrocarbon-nucleoside adduct derived from mouse skin treated with the parent compound in vivo. The structures of certain others of the metabolites produced in vitro are also considered.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005260:Female; D006067:Gonanes / Q000378:metabolism* / Q000633:toxicity; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009153:Mutagens; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D006067:Gonanes; D009153:Mutagens; C043381:15,16-dihydro-1,11-methanocyclopenta(a)phenanthren-17-one; D004247:DNA