Effects of heterocyclic amines with mammary gland carcinogenic potential on estrogenic response of uterus in ovariectomized rats

Heterocyclic amines (HCAs) present in cooked foods are suggested to be invo lved in human breast cancer development. Estrogen plays a pivotal role in m ammary gland carcinogenesis. Therefore, we designed an in vivo experiment t o investigate potential estrogenic effects of two HCAs, 2-amino-3-methylimi dazo [4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyrid ine (PhIP), which induce mammary gland cancers in rodents, on the uterus of ovariectomized (OVX) Sprague-Dawley (SD) rats. Female SD rats ovariectomiz ed at 35 days of age were given intraperitoneal injections of 17 beta -estr adiol (E2) at doses of 0, 30 or 50 mug/kg or one of the HCAs at a dose of 5 0 mg/kg b.w. once a day at 47, 48, and 49 days of age. E2 dramatically incr eased uterine weights, stromal thickness, epithelial cell height, and 5-bro mo-2'-deoxyuridine (BrdU) positive cell counts in a dose dependent manner. Intraperitoneal administration of PhIP or IQ, in contrast, did not produce any estrogenic responses in this assay system. These results indicate that the carcinogenicities of these two HCAs in mammary glands are not associate d with estrogenic potential. (C) 2001 Elsevier Science Ireland Ltd. All rig hts reserved.