Carcinogenic effect of 1-butyl-1-nitrosourea on female Sprague-Dawley rats

Carcinogenic effect of a single oral administration of 300 or 200 mg/kg body weight of 1-butyl-1-nitrosourea (BNU) and continuous oral administration of 400 ppm solution of BNU in the drinking water for 5, 10, 15, and 20 weeks to female SD rats was studied. In addition, the number of spleen cells capable of forming plaques (PFC) against primary immunization with sheep red blood cells was investigated in various stages of the animal experiments. With a single oral administration of BNU, tumors developed in 31/50 (62%) rats between the 25th and 75th week. They were most frequently seen in the mammary gland (40%), followed by the stomach (10%), kidneys (8%), and ovary (8%). Leukemia was found in 8%. No dose-effect relationship was observed in these 2 experimental groups. On the other hand, tumors developed in 67/77 (88%) of the rats that received BNU in their drinking water. The incidence of tumors was highest in leukemia (61%), followed by mammary tumors (26%), intestinal tumors (12%), and ear duct tumors (8%). There was a dose-effect relationship among the 4 groups in the latent period and target organs for tumor development. Although the PFC count of the rats receiving BNU for 5 weeks recovered gradually to about 50% of the control level at the end of the 25th experimental week, it remained less than 10% of the control level for the whole experimental period in those receiving BNU longer than 10 weeks. Therefore, it was apparent that the tumors developed, proliferated, and finally killed the host rats in highly immunosuppressive state.