Evidence for bay region activation of chrysene 1,2-dihydrodiol to an ultimate carcinogen.
The tumor-initiating activities of chrysene and the three metabolically possible trans-dihydrodiols at the 1,2-, 3,4-, and 5,6-positions of chyrsene were determined on the skin of female CD-1 mice. A single topical application of 0.4, 1.25, or 4.0 mumol of each compound was followed 7 days later by twice-weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate for 25 weeks. The most potent tumor initiator was chrysene 1,2-dihydrodiol, which had approximately twice the tumorigenic activity of the parent hydrocarbon chrysene at all doses tested. Chrysene 3,4-dihydrodiol and chrysene 5,6-dihydrodiol had no significant tumorigenic activity. 1,2-Dihydroxy-1,2,3,4-tetrahydrochrysene, a compound related to chrysene 1,2-dihydrodiol but with the conjugated nonaromatic double bond removed from the 3,4-position of the molecule, had less than 25% of the tumorigenic activity of chrysene 1,2-dihydrodiol. These results indicate that chrysene 1,2-dihydrodiol is a proximate carcinogenic metabolite of chrysene and that a chrysene 1,2-diol-3,4-epoxide, in which the epoxide group forms part of the bay region in the molecule, is a likely candidate as an ultimate carcinogenic metabolite of chrysene.
D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D002911:Chrysenes / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010616:Phenanthrenes / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D002911:Chrysenes; D010616:Phenanthrenes