MUTAGENIC AND CARCINOGENIC METABOLITES OF THE CARCINOGEN 15, 16-DIHYDRO-11-METHYLCYCLOPENTA[A]PHENANTHREN-17-ONE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 882-886
Abstract
Microsomal metabolites of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one (structure I) were separated by high-pressure liquid chromatography and their structures were established on the basis of UV and mass spectra together with considerations of their general chemical properties. This was assisted by comparisons with metabolites formed in the same way from the synthetic 15-hydroxy (structure III), 16-hydroxy (structure II), and 11-hydroxymethyl (structure IV) derivatives, which themselves occur as metabolites of structure I. Products derived from attack at the 2 benzo-ring double bonds occurred, but no K-region products were found. Only metabolites having a non-bay region 3,4-dihydrodiol system were mutagenic and bound to DNA after in vitro microsomal activation. The 3,4-dihydro-3,4-diol (metabolite e) was the main form and the 3,4-diols of the monools (structures II to IV) were minor proximate forms of this carcinogen. In a 2-stage experiment, the synthetic 16-ol (structure II) was almost as carcinogenic as structure I itself in mice; the 15-ol (structure III) and 11-hydroxymethyl derivative (structure IV) were much less active. The same order was also observed in the mutagenicity of these compounds in the Ames test [using Salmonella typhimurium].

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