The rat urinary bladder as a new target of heterocyclic amine carcinogenicity: tumor induction by 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate.

In order to examine the carcinogenicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2), 30 male and 30 female F344 rats were maintained on diet containing 0, 30, or 100 ppm Trp-P-2 for 112 weeks. The overall mean chemical intakes in the 100 ppm and 30 ppm groups were 3.84 and 1.14 mg/kg/day in males, and 4.57 and 1.34 mg/kg/day in females, respectively. Females of the 100 ppm group showed increased mortality in the late period of the study. In the 100 ppm group, significant increases in the incidences of neoplastic lesions were found in the liver, urinary bladder and mammary gland in males, and in the mammary gland, hematopoietic system and clitoral gland in females. Histologically, tumors induced by Trp-P-2 were hepatocellular adenomas, transitional cell tumors (papillomas and carcinomas) of the urinary bladder, fibroadenomas/fibromas of the mammary gland, malignant lymphomas and clitoral gland tumors (adenomas and adenocarcinomas). These results indicate multi-target carcinogenicity of Trp-P-2 in F344 rats and provide evidence that the urinary bladder is also a target for heterocyclic amine action.