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.