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 anti-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), a fjord region diol-epoxide, and anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, a bay region diol-epoxide, were applied at total doses of 12.2 mumol. 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-dihydroxy-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.
Hecht
S S
SS
American Health Foundation, Valhalla, New York 10595.
el-Bayoumy
K
K
Rivenson
A
A
Amin
S
S
D000230:Adenocarcinoma / Q000139:chemically induced; D000818:Animals; D001564:Benzo(a)pyrene / Q000737:chemistry / Q000633:toxicity*; D004852:Epoxy Compounds / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D018226:Fibroadenoma / Q000139:chemically induced; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D010616:Phenanthrenes / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D010616:Phenanthrenes; D001564:Benzo(a)pyrene; C002615:benzo(c)phenanthrene