MAMMARY CARCINOGENICITY OF DIOL EPOXIDE METABOLITES OF BENZO[J]FLUORANTHENE IN FEMALE CD RATS

The mammary carcinogenicity of two diol epoxide metabolites of the com monly occurring environmental carcinogen benzo[j]fluoranthene (BjF) wa s investigated by direct application to the tissue beneath the mammary glands of female CD rats. The compounds tested were 5-dihydroxy-anti- 6,6a-epoxy-4,5,6,6a-tetrahydroBjF (BjF-4,5-DE) and ihydroxy-anti-11,12 -epoxy-9,10,11,12-tetrahydroBjF (BjF-9,10-DE). The positive control wa s i-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE). Groups o f 20 female CD rats were maintained on AIN-76A-based high fat diet (23 .5% corn oil) and at age 30 days were given three injections of 0.2 mu mol of each compound in 0.1 mi dimethyl sulfoxide (DMSO), or DMSO alo ne, in the tissue underlying each of the three left thoracic nipples. The three right nipple areas were injected with DMSO alone. On the nex t day, each rat received three injections of 0.2 mu mol of each compou nd in 0.1 ml DMSO, or DMSO alone, under each of the three left inguina l nipples, and DMSO alone under the three right nipples. The experimen t was terminated after 44 weeks. BjF-9,10-DE, mean latent period 21.0 +/- 8.8 weeks, was more active than BjF-4,5-DE, mean latent period 36. 2 +/- 8.0 weeks. BjF-9,10-DE induced tumors in 70% of the rats; a tota l of 38 fibroadenomas and eight adenocarcinomas was observed. BjF-4,5- DE induced tumors in 55% of the rats. These included 17 fibroadenomas, seven dysplastic fibroadenomas, and two adenocarcinomas, BcPDE induce d tumors rapidly, with a mean latent period of 9.7 +/- 4.0 weeks. All BcPDE-treated rats had mammary tumors. A total of 46 adenocarcinomas, as well as other tumors, were observed. In the DMSO-treated rats, mamm ary tumor incidence was 15%. The results of this study demonstrate tha t BjF-9,10-DE is more carcinogenic in the rat mammary gland than BjF-4 ,5-DE and that low doses of both diol epoxide metabolites of BjF are e ffective mammary tumorigens in female C rats maintained on a high fat diet.