Foster Warren G, Younglai Edward V, Boutross-Tadross Odette, Hughes Claude L, Wade Michael G
Department of Obstetrics and Gynecology, McMaster University and Health Sciences Centre, Hamilton, Ontario, Canada.
Toxicol Sci. 2004 Jan;77(1):91-100. doi: 10.1093/toxsci/kfg247. Epub 2003 Sep 26.
In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group received either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist, blinded to treatment groups, examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively, our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.
在一项相关的生殖毒理学研究中，旨在调查子宫内暴露于环境毒物以及与产后染料木黄酮的潜在相互作用的影响，在200日龄的雌性后代中观察到胸乳腺明显增大。因此，本研究的目的是分析子宫内暴露于毒物混合物对乳腺形态的影响。通过定时交配的斯普拉格-道利大鼠在妊娠第9至16天接受赋形剂或环境毒物混合物处理，剂量为可接受每日摄入量的1倍。此外，尚不清楚大豆配方奶粉中植物雌激素的产后暴露是否对乳腺癌有益或有风险，并且与环境毒物的潜在相互作用尚不清楚。因此，每个处理组的一半雌性幼崽在出生后第2至8天接受皮下赋形剂或染料木黄酮（10微克/克体重/天）处理。在200日龄处死后，一名对处理组不知情的病理学家检查了乳腺组织病理学。在子宫内暴露于混合物的大鼠乳腺中仅发现轻度组织学变化，而在染料木黄酮组的乳腺中观察到明显的导管增生、泌乳变化和纤维化，在混合物+染料木黄酮组中更明显。对照组的乳腺组织学正常。总体而言，我们的结果表明，产后暴露于药理水平的染料木黄酮会在成年雌性大鼠乳腺中诱导深刻的形态学变化，并且高水平的植物雌激素具有调节毒物混合物毒理学效应的潜力。
