We examined the mammary carcinogenicity in CD rats of anti-2,3-dihydroxy-1,10b-epoxy-10b, 1,2,3-tetrahydrofluoranthene (FDE), a genotoxic metabolite of the environmental pollutant fluoranthene. FDE (2 μmol or 10 μmol) 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 μmol 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 annuals (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.
Bibliographical noteFunding Information:
This study was supported by Grant No. CA-44377 from the National Cancer Institute. The bioassay was carried out in the American Health Foundation Research Animal Facility, supported partially by Cancer Center Support Grant CA-17613 from the National Cancer Institute. We thank Chang-In Choi for his advice and assistance with this study. This is paper no. 157 in 'A Study of Chemical Carcinogenesis'.