Carcinogenic effects of a mixture of nitropyrenes in F344 rats following its repeated oral administrations.

The carcinogenic effects of a mixture of 1-nitropyrene and three dinitropyrenes (1,3-, 1,6- and 1,8-dinitropyrene) were investigated in rats. Female F344/Jcl rats were given one of three doses (5, 10 and 20 mg/kg body weight) of the mixture by repeated intragastric instillations twice a week for 55 weeks, and then autopsied 49 weeks later. Mammary adenocarcinomas were induced in rats of all the three experimental groups dose-dependently, while no adenocarcinoma was induced in the control rats which were given only vehicle. Clitoral gland tumors, most of which were diagnosed as squamous cell carcinomas, were also commonly observed in the NP-treated rats in a dose-dependent way. In addition, high incidences of mononuclear cell leukemias were noted in the NP-treated rats. Other tumors were frequently induced in the uterus and endocrine organs, such as the pituitary, adrenal, and thyroid glands. However, the incidences of these tumors were almost equal in both the control and NP-treated groups. The results of the present study indicated the potential carcinogenic activities of nitropyrene compounds in female rats when they were treated by oral route, and suggest that the oral intake of nitropyrene compounds might be related to the incidence of cancer in humans.