Equivocal impact of transplacental and lactational exposure to a food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, on prostate and colon lesion development in F344 rats.
The carcinogenic potential of maternal dietary exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was investigated with the focus on the prostate and mammary glands and colons of the offspring. PhIP-DNA adducts were immunohistochemically detected in all three organs of 3-week-old animals after dams had received 200 ppm PhIP in the diet from 4 weeks before mating to weaning. The sites were essentially the same as in adult rats, suggesting that the distribution of bioactivating enzymes for PhIP do not differ greatly. Ki-67 labeling indices were increased only in the colons of the female offspring at 3-weeks of age. Development of preneoplastic and neoplastic lesions in the prostate and colon was not enhanced when the rats were maintained on PhIP-free diet until 63 weeks of age, except for significant increase in multiplicity of aberrant crypt foci in the females. The present findings indicate that PhIP exposure via placenta and breast milk may be important but that high doses and long periods may be necessary for tumor development.
Ikeda
Yoshihisa
Y
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Cho
Young-Man
YM
Takahashi
Satoru
S
Tang
Mingxi
M
Asamoto
Makoto
M
Ogawa
Kumiko
K
Shirai
Tomoyuki
T
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D003108:Colonic Diseases / Q000139:chemically induced / Q000662:veterinary; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000662:veterinary; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000737:chemistry; D011230:Precancerous Conditions / Q000139:chemically induced / Q000662:veterinary; D011247:Pregnancy; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000662:veterinary; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D002273:Carcinogens; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine