High susceptibility of the ACI and spontaneously hypertensive rat (SHR) strains to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) prostate carcinogenesis

Carcinogenic responses in the prostate to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were compared among seven rat strains (F344, ACl, Spontaneously Hypertensive Rat (SHR), Sprague-Dawley (SD), Wistar, Lewis and Brown Norway (BN)). Ten-week-old animals of each strain were given PhIP at 400 ppm in the diet for 20 weeks then maintained until week 54. The final survival rates were 92, 92, 83, 75, 67, 42 and 42%, respectively, and the SHR strain showed the highest sensitivity with regard to development of prostatic intraepithelial neoplasias (PINS) in the ventral prostate. With regard to the induction of adenocarcinomas of the ventral prostate, the ACl strain was most sensitive, whereas Lewis and F344 rats were relatively resistant. No adenocarcinomas were found in the dorsolateral or anterior prostate or seminal vesicles in any of the strains. The levels of serum testosterone and estrogen, PhIP-DNA adducts and cell kinetics did not correlate with the development of ventral prostatic lesions and thus other factors are presumably responsible for the variations in susceptibility. The present data indicate that ACl and SHR rats are appropriate strains for experimental investigation of PhIP-induced prostate carcinogenesis.