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Tumor-initiating Activity of Dihydrodiols Formed Metabolically from 5-Methylchrysene¹

Division of Environmental Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595

The major dihydrodiols formed from 5-methylchrysene by rat liver 9000 x g supernatant were tested for tumor-initiating activity on mouse skin. The compounds tested were 1,2-dihydro-1,2-dihydroxy-5-methylchrysene, 7,8-dihydro-7,8-dihydroxy-5-methylchrysene, 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, and 5-methylchrysene. Each compound was applied in a total initiating dose of 30 µg and was followed by promotion with tetradecanoylphorbol acetate. 1,2-Dihydro-1,2-dihydroxy-5-methylchrysene was the most powerful tumor initiator, inducing tumors in 95% of the animals and 7.3 tumors per animal. 5-Methylchrysene and 7,8-dihydro-7,8-dihydroxy-5-methylchrysene induced tumors in 75 and 50% of the animals and gave 3.0 and 1.1 tumors per animal, respectively. 9,10-Dihydro-9,10-dihydroxy-5-methylchrysene was not tumorigenic. The results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate carcinogen of 5-methylchrysene. Both 1,2-dihydro-1,2-dihydroxy-5-methylchrysene and 7,8-dihydro-7,8-dihydroxy-5-methylchrysene can theoretically form bay-region dihydrodiol epoxides, but the former was more tumorigenic than the latter. The high activity of 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is typical of hydrocarbon derivatives with a methyl group in the bay region adjacent to an unsubstituted angular ring.

¹ This study was supported by Grant CA-012376 from the National Cancer Institute. This is Paper 24 of the series, "A Study of Chemical Carcinogenesis."

² Recipient of National Cancer Institute Research Career Development Award 5K04 CA-00124. To whom requests for reprints should be addressed.

Received 10/11/79. Accepted 1/23/80.