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Increased Risk of Mammary Carcinoma Development following Transplacental and Trans-Breast Milk Exposure to a Food-derived Carcinogen, 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in Sprague-Dawley Rats¹

First Department of Pathology, Nagoya City University Medical School [R. H., J. K., M. Y., S. T., T. K., Mi. F., T. Sh.] and Nagoya City University [N. I.], 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, and Biochemistry Division, National Cancer Center Research Institute [Ma. F., K. F., K. W.] and National Cancer Center [T. Su.], 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan

Effects of transplacental and trans-breast milk exposure to a food-derived mammary and colon carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), were investigated in rats. Female Sprague-Dawley rats were administered PhIP in the diet (100 ppm) for 4 weeks before mating with nontreated males and also during gestation and lactation. As controls, additional females were maintained on the basal diet without PhIP and mated as with the treated animals. The offspring of both groups were subdivided for each sex at weaning into three dietary groups receiving 100, 25, and 0 ppm and were killed at 47 weeks of age. Effects of the transplacental and neonatal exposure to PhIP on mammary carcinogenesis were most evident in females administered 25 ppm PhIP after weaning; the incidence and multiplicity of adenocarcinomas in offspring from the PhIP fed dams (42.9%, 0.62/rat) was significantly higher than the value for offspring from nontreated dams (4.8%, 0.05/rat). Furthermore, in the basal diet groups, the incidence of adenocarcinomas in females was higher, albeit not significantly, in offspring of the PhIP-treated than the nontreated dams (16.7%, 0.22/rat as compared with 3.3%, 0.07/rat). Although the highest incidence of mammary adenocarcinomas was found in the female progeny given 100 ppm PhIP from PhIP-treated dams (70.0%, 1.55/rat), this was only slightly higher than the 61.9% and 0.90/rat of the same dose group from the nontreated dams. In males, no apparent effects of transplacental and neonatal exposures were evident. In a separate experiment, excretion of PhIP into breast milk and transfer of PhIP to fetuses and neonates with resultant hepatic PhIP-DNA adduct formation were demonstrated. Thus, maternal exposure to this food-derived carcinogen may be a critical risk factor for generation of mammary carcinomas.

¹ Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, and the Ministry of Health and Welfare of Japan, and grants from the Society for Promotion of Pathology of Nagoya, Japan.

² To whom requests for reprints should be addressed.

Received 6/ 8/95. Accepted 8/ 2/95.

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