This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Levin, W. Articles by Conney, A. H. Search for Related Content PubMed PubMed Citation Articles by Levin, W. Articles by Conney, A. H.

Evidence for Bay Region Activation of Chrysene 1,2-Dihydrodiol to an Ultimate Carcinogen

Department of Biochemistry and Drug Metabolism, Hoffman-LaRoche Inc., Nutley, New Jersey 07110 [W. L., A. W. W., R. L. C., A. H. C.], and Section on Oxidation Mechanisms, Laboratory of Chemistry, National Institute of Arthritis, Metabolism and Digestive Diseases, NIH, Bethesda, Maryland 20014 [H. Y., H. D. M., D. M. J.]

The tumor-initiating activities of chrysene and the three metabolically possible trans-dihydrodiols at the 1,2-, 3,4-, and 5,6-positions of chrysene were determined on the skin of female CD-1 mice. A single topical application of 0.4, 1.25, or 4.0 µmol 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.

¹ To whom requests for reprints should be addressed.