Journal of Steroid Biochemistry & Molecular Biology, 2012, 129(3–5):191-200.

Endocrine-active chemicals in mammary cancer causation and prevention

Sarah Jenkins, Angela M. Betancourt, Jun Wang, et al

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, United States; UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, United States

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'.

英国《类固醇生物化学与分子生物学杂志》，2012年4月

用于乳腺癌诱发及防治的内分泌活性化学物质

莎拉 詹金斯，安吉拉 M 贝当古，王俊，等

美国阿拉巴马大学伯明翰分校药理学和毒理学学院和UAB 综合癌症中心

内分泌活性化学物质改变或模仿生理激素。据报道，这些化合物来自各种各样的资源，并且最近的研究表明人体普遍接触这些化合物的几种。在人体乳腺癌诱因中，性类固醇激素，雌激素等可以干扰雌激素信号通路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，本综述的目的是考察几种常见的内分泌活性物质及其在乳腺癌癌症诱发或预防中各自的作用。塑料成分双酚 A (BPA)，人工合成的雌激素己烯雌酚 (DES)，有机燃烧副产物2,3,7,8 四-二苯并二恶英 (TCDD)， 大豆组分金雀异黄素，和红葡萄植物抗毒素白藜芦醇，每一种和雌二醇的结构有某种程度上的相似。然而，尽管这些结构相似，这些化学成分的每一种在体外和体内乳腺癌诱发和预防的差异较大。生命早期接触BPA和 DES 增加了啮齿动物因化学方法诱导发生乳腺癌变的风险，大概是通过正常乳腺成熟的迟滞和/或破坏乳腺组织中细胞增殖和凋亡的比例。另一方面，早期接触金雀异黄素及白藜芦醇可以保护啮齿动物不受化学诱导和自发性乳腺癌的威胁。有趣的是，TCDD，在结构上最不同于上述化学成分的一种抗雌激素，也通过乳腺成熟发育迟滞增加了化学诱导乳腺癌变的危险。这篇文章是特定主题为“内分泌干扰物”的一部分。