Dose-dependent induction of mammary carcinomas in female Sprague-Dawley rats with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

The dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) induction of mammary carcinomas was investigated in female Sprague-Dawley (SD) rats given PhIP in the diet for 48 weeks at concentrations of 0, 25, 100 and 200 ppm in experiment 1, and 0, 12.5, 50 in experiment 2. Yields of ductular lesions, including intraductal papillomas and carcinomas, as well as papillo-tubular and solid-tubular carcinomas, showed dependence on the dose, with the respective total incidences being 0, 4.8, 25, 72.2 and 0, 10 and 35%. There was thus no apparent carcinogen exposure threshold. The present results confirmed the carcinogenicity demonstrated in a previous study using F344 rats and revealed the SD rat strain to be more susceptible.