The carcinogenicity of 15,16-dihydro-11-methyl-cyclopenta[a]phenanthren-17-one

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Abstract
Direct comparison of skin-tumor induction by 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one (I) and by benzo[a]pyrene on mouse skin, by repeated application or by initiation with a single dose followed by promotion with croton oil, demonstrated that these 2 carcinogens have similar potency. After repeated application of (I) the mean latent period for skin-tumor induction was linearly related to the logarithm of the dose over a 10-fold dose range. Under these conditions, application of the aryl-hydrocarbon-hydroxylase inhibitor 7,8-benzoflavone together with (I) inhibited tumor induction by about 40%. By contrast, in the 2-stage experiment, little effect on tumor incidence or latent period was observed when this inhibitor was applied with the single initiating dose of (I). Coadministration of the epoxide-hydratase inhibitor 1,1,1-trichloropropene oxide caused enhancement by shorting the latent period. After s.c. injection of (I) into mice, a similar number of tumors was induced on skin remote from the site of injection by promotion with croton oil begun 1 wk or 6 mo. after initiation. Gastric instillation of (I) into female rats induced mammary adenocarcinomas.

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