Tumor-initiating activity of dihydrodiols formed metabolically from 5-methylchrysene.
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 microgram 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.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002277:Carcinoma / Q000139:chemically induced; D002911:Chrysenes / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D010212:Papilloma / Q000139:chemically induced; D010616:Phenanthrenes / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship
D002273:Carcinogens; D002911:Chrysenes; D010616:Phenanthrenes; C017229:1,2-dihydro-1,2-dihydroxy-5-methylchrysene; C024351:9,10-dihydro-9,10-dihydroxy-5-methylchrysene; C024350:7,8-dihydro-7,8-dihydroxy-5-methylchrysene; C008422:5-methylchrysene