Potent Mammary Carcinogenicity in Female CD Rats of a Fjord Region Diol-Epoxide of Benzo[c]phenanthrene Compared to a Bay Region Diol-Epoxide of Benzo[a]pyrene

Two diol-epoxide metabolites of benzo[c]phenanthrene and benzo[a]-pyrene, polynuclear aromatic hydrocarbons which occur in the environment, were tested for carcinogenicity by direct injection into the mammary fat pads of female CD rats. The compounds a/i-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), a fjord region diol-epoxide, and anft′-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene, a bay region diol-epoxide, were applied at total doses of 12.2 fimol. 6-Nitrochrysene was applied at the same dose as a positive control (K. El-Bayoumy, A., Rivenson, P., Upadhyaya, Y. H. Chae, and S. S. Hecht, Cancer Res. 53: 3719-3722, 1993). The sterically hindered fjord region diol-epoxide BcPDE was a powerful mammary tumorigen and carcinogen, rapidly inducing significantly more fibroadenoma and adenocarcinoma than either of the other compounds. Anti-7,8-dibydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was a weaker mammary tumorigen than BcPDE and 6-nitrochrysene. The results of this study provide the first evidence for mammary tumorigenicity of polynuclear aromatic hydrocarbon diol-epoxides and demonstrate the potent mammary carcinogenicity of BcPDE.