High susceptibility of the ACI and spontaneously hypertensive rat (SHR) strains to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) 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, ACI, 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 ACI 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 ACI and SHR rats are appropriate strains for experimental investigation of PhIP-induced prostate carcinogenesis.
Inaguma
Shingo
S
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601. sinaguma@med.nagoya-cu.ac.jp
Takahashi
Satoru
S
Ohnishi
Hiroyuki
H
Suzuki
Shugo
S
Cho
Young-Man
YM
Shirai
Tomoyuki
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology; D018736:DNA Adducts; D018450:Disease Progression; D004198:Disease Susceptibility; D006728:Hormones / Q000097:blood; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D019048:Prostatic Intraepithelial Neoplasia / Q000139:chemically induced / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015996:Survival Rate
D002273:Carcinogens; D018736:DNA Adducts; D006728:Hormones; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine