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]-pyre ne, polynuclear aromatic hydrocarbons which occur in the environment, were tested for carcinogenicity by direct injection into the mammary f at pads of female CD rats. The compounds y-1,2-epoxy-1,2,3,4-tetrahydr obenzo[c]phenanthrene (BcPDE), a fjord region diol-epoxide, and oxy-9, 10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene, a bay region diol-epoxide , were applied at total doses of 12.2 mumol. 6-Nitrochrysene was appli ed 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 p owerful mammary tumorigen and carcinogen, rapidly inducing significant ly more fibroadenoma and adenocarcinoma than either of the other compo unds. droxy-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 polynuc lear aromatic hydrocarbon diol-epoxides and demonstrate the potent mam mary carcinogenicity of BcPDE.