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 knowninducers of mammary cancer in rodents can be regarded as potentialcauses of human cancer and need to be evaluated more completely.Therefore, the purpose of this study was to determine underidentical conditions the relative carcinogenic potency in themammary glands of rats of benzo[a]pyrene (B[a]P), 1-nitropyrene(1-NP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyidne (PhIP).Thirty-day-old female CD rats were gavaged once weekly for 8weeks with B[a]P, 1-NP or PhIP. Each compound was given at 50µmol/rat/week in 0.5 ml trioctanoin for a total dose of400 µmoul/rat. Forty-one weeks after the last carcinogenadministration, rats were killed. In the 1-NP-treated rats,treatment elicited primarily benign tumors. In contrast, theB[a]P- and PhIP-treated rats developed both malignant and benigntumors. The incidence of adenocarcinomas in rats treated withB[a]P or PhIP was comparable and significantly higher than thatin animals receiving trioctanoin only. The incidence of benigntumors (fibroadenomas, desmoplastic adenomas and adenomas) observedin animals treated with B[a]P or 1-NP was comparable and significantlyhigher than that in animals given PhIP or trioctanoin. Thisis the first report describing the carcinogenic activity ofPhIP, given by gavage, in the mammary gland of CD rats and rankingthe carcinogenic potency observed under identical conditions,of three agents (B[a]P