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 o f mammary cancer in rodents can be regarded as potential causes of hum an cancer and need to be evaluated more completely. Therefore, the pur pose of this study was to determine under identical conditions the rel ative carcinogenic potency in the mammary glands of rats of benzo[a]py rene (B[a]P), 1-nitropyrene (1-NP) and 2-amino-1-methyl-6-phenylimidaz o[4,5-b]p (PhIP). Thirty-day-old female CD rats were gavaged once week ly for 8 weeks nith B[a]P, 1-NP or PhIP. Each compound was given at 50 mu mol/rat/week in 0.5 ml trioctanoin for a total dose of 400 mu mol/ rat. Forty-one weeks after the last carcinogen administration, rats we re killed. In the 1-NP-treated rats, treatment elicited primarily beni gn tumors. In contrast, the B[a]P- and PhIP-treated rats developed bot h malignant and benign tumors. The incidence of adenocarcinomas in rat s treated with B[a]P or PhIP was comparable and significantly higher t han that in animals receiving trioctanoin only. The incidence of benig n 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 fi rst report describing the carcinogenic activity of PhIP, given by gava ge, in the mammary gland of CD rats and ranking the carcinogenic poten cy observed under identical conditions, of three agents (B[a]P similar or equal to PhIP > 1-NP) that are prevalent in the human environment.