Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats.

Agents that are ubiquitous in the environment and are known inducers of mammary cancer in rodents can be regarded as potential causes of human cancer and need to be evaluated more completely. Therefore, the purpose of this study was to determine under identical conditions the relative carcinogenic potency in the mammary glands of rats of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Thirty-day-old female CD rats were gavaged once weekly for 8 weeks with B[a]P, 1-NP or PhIP. Each compound was given at 50 mumol/rat/week in 0.5 ml trioctanoin for a total dose of 400 mumol/rat. Forty-one weeks after the last carcinogen administration, rats were killed. In the 1-NP-treated rats, treatment elicited primarily benign tumors. In contrast, the B[a]P- and PhIP-treated rats developed both malignant and benign tumors. The incidence of adenocarcinomas in rats treated with B[a]P or PhIP was comparable and significantly higher than that in animals receiving trioctanoin only. The incidence of benign tumors (fibroadenomas, desmoplastic adenomas and adenomas) observed in animals treated with B[a]P or 1-NP was comparable and significantly higher than that in animals given PhIP or trioctanoin. This is the first report describing the carcinogenic activity of PhIP, given by gavage, in the mammary gland of CD rats and ranking the carcinogenic potency observed under identical conditions, of three agents (B[a]P congruent to PhIP > 1-NP) that are prevalent in the human environment.