The biological activity and activation of 15,l6-dihydro-1,11-methanocyclopenta [a] penanthren-17-one, a carcinogen with an obstructed bay region

• Published in: Carcinogenesis (New York) 1984-11, Vol.5 (11), p.1485-1490
• Main Authors: Hadfield, Stephen T., Bhatt, Tarlochan S., Coombs, Maurine M.
• Format: Article
• Language: English
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/5.11.1485

The proposal that an unobstructed bay region is a prerequisite for tumorigenic activity in cydopenta[a]phenanthrene-17-ones is not supported by the observation of the tumorigenicity of 15,16-dihydro-1,ll-methanocydopenta[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-3,4dihydrodiol-anti-l,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 metabolite produced in vitro are also considered.