CARCINOGENICITY OF A MUTAGENIC COMPOUND FROM FOOD, 2-AMINO-3-METHYL-9H-PYRIDO[2,3-B]INDOLE (MEA-ALPHA-C), IN MALE F344 RATS

Carcinogenicity of 2-amino-3-methyl-9H-pyrido[2,3-b]-indole (MeA alpha C) was investigated at dietary levels of 0 (control), 0.01, 0.02, 0.04 and 0.08% using male F344/DuCrj rats. The administration of MeA alpha C was continued for 100 experimental weeks for the control, 0.01 and 0.02% groups, but halted after 52 and 26 experimental weeks for the 0.04 and 0.08% groups respectively due to severe toxicity. Well-differentiated hepatocellular carcinomas, lacking in control animals, were induced in 5/20 rats (25%) and 6/20 rats (30%) of the 0.01% and 0.02% groups respectively. Pancreatic acinar cell adenomas were also significantly increased in the 0.01% (30%) and 0.02% (40%) groups, in association with high incidences of hyperplastic lesions of acinar cells. Fibromas in the subcutis developed at a high incidence (70%) in the 0.02% group. MeA alpha C was also suggested to elicit fibrosarcomas in the salivary gland and transitional cell carcinomas in the urinary bladder. Among the non-neoplastic lesions, severe atrophy of the salivary glands and pancreas and severe renal toxicity were noteworthy. In conclusion, MeA alpha C is a multi-targeting carcinogen in rats, similar in this respect to other heterocyclic amines,