Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):191-200. doi: 10.1016/j.jsbmb.2011.06.003. Epub 2011 Jun 23.
Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'.
内分泌活性化学物质会改变或模拟生理激素。这些化合物据称来自多种来源，最近的研究表明，人类广泛接触到其中的几种化合物。鉴于甾体激素雌激素在人类乳腺癌发病机制中的作用，干扰雌激素信号传导的内分泌活性化学物质是导致乳腺癌高发的一个潜在因素。因此，本综述的目的是研究几种常见的内分泌活性化学物质及其在乳腺癌发病或预防中的各自作用。塑料成分双酚 A（BPA）、合成雌激素己烯雌酚（DES）、有机燃烧的副产物 2,3,7,8-四氯二苯并对二恶英（TCDD）、大豆成分染料木黄酮和红葡萄植物抗毒素白藜芦醇在结构上与雌激素具有一定程度的相似性。然而，尽管这些化学物质在结构上具有相似性，但它们在体外和体内的性质在乳腺癌发病和预防方面却有很大的不同。BPA 和 DES 的早期生命暴露会增加啮齿动物对化学诱导性乳腺癌的易感性，这可能是通过延迟正常乳腺成熟和/或破坏乳腺中细胞增殖和凋亡的比例来实现的。另一方面，早期接触染料木黄酮和白藜芦醇可保护啮齿动物免受化学诱导和自发性乳腺癌的侵害。据报道，这是通过染料木黄酮和白藜芦醇加速乳腺成熟的能力来实现的。有趣的是，与上述化学物质结构最不相似且作为抗雌激素的 TCDD 也通过延迟乳腺成熟来增加化学诱导的乳腺癌发生。本文是特刊“内分泌干扰物”的一部分。
