Mammary carcinogenicity in female CD rats of a diol epoxide metabolite of fluoranthene, a commonly occurring environmental pollutant.

We examined the mammary carcinogenicity in CD rats of anti-2,3-dihydroxy-1,10b-epoxy-10b,1,2,3-tetrahydro-fluoranthene (FDE), a genotoxic metabolite of the environmental pollutant fluoranthene. FDE (2 mumol or 10 mumol) in 0.1 ml dimethyl sulfoxide (DMSO) was injected beneath each of the three left thoracic nipples of groups of 20 rats each, with 0.1 ml DMSO alone being injected under the right nipples. On the next day, the procedure was repeated for the three inguinal nipples on each side. anti-3,4-Dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]-phenanthrene (BcPDE, 2 mumol per nipple) was used as a positive control and DMSO alone as a negative control. Tumor development was assessed weekly by palpation and the experiment was terminated after 41 weeks. Eighty five percent of the rats in each of the FDE treated groups developed histologically confirmed mammary tumors, compared to 11% in the DMSO treated animals (P < 0.01). Most tumors were on the left side. The lower dose of FDE induced a significant number of adenomas while the higher dose induced significant incidences of both adenomas and adenocarcinomas compared to controls. BcPDE was a powerful mammary carcinogen, confirming our previous observation. The results of this study demonstrate the carcinogenicity of FDE to the CD rat mammary gland. Since FDE is a potentially transportable human metabolite of fluoranthene, its possible role as an etiologic factor in breast cancer deserves further study.