美国的一项新研究发现，已被禁止用于婴儿奶瓶的双酚A和常用于化妆品防腐剂的羟苯甲酯会干扰乳腺癌药物的治疗效果。
位于旧金山的加利福尼亚州太平洋医学中心的研究人员发现，从乳腺癌高危患者体内提取的乳腺细胞在实验室中与双酚A和羟苯甲酯接触后，便可能变得有能力对抗乳腺癌治疗药物。该研究成果已发表在英国学术期刊《致癌作用》（Carcinogenesis）网络版上。
这项研究的负责人古德森介绍说，他莫西芬是目前治疗女性乳腺癌的标准药物，也是男性乳腺癌治疗使用最多的药物，可以减慢正常及癌变乳腺细胞的生长，最终导致细胞死亡。然而被上述两种化学物质污染的乳腺细胞在他莫西芬面前显得异常“骁勇善战”，没有死亡而是持续生长。
这一发现再次为双酚A及羟苯甲酯的危害提供了证据。双酚A被广泛用于食品容器、家用电器和购物收据用纸中。羟苯甲酯虽然不为公众所熟知，却被广泛用作化妆品等个人护理产品的防腐剂，美国食品和药物管理局目前认为羟苯甲酯对公众健康没有威胁。
古德森表示，双酚A和羟苯甲酯由于应用广泛，人们在日常生活中很难避免接触。它们都具有类激素作用，有可能模拟雌激素对机体的危害，甚至比自然激素更难对付。太平洋医学中心的研究人员尚不清楚这两种物质对人体的影响是否可逆，但认为管理部门应当要求减少对它们的使用。（生物谷 Bioon.com）
doi:10.1093/carcin/bgr196
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Activation of the mTOR Pathway By Low Levels of Xenoestrogens in Breast Epithelial Cells From High-Risk Women
William H. Goodson III, Maria Gloria Luciani, Aejaz Sayeed, Ian Jaffee, Dan H. Moore II1, and Shanaz H. Dairkee
Breast cancer is an estrogen driven disease. Consequently, hormone replacement therapy (HRT) correlates with disease incidence. However, increasing male breast cancer rates over the past three decades implicate additional sources of estrogenic exposure including wide spread estrogen-mimicking chemicals or xenoestrogens (XEs), such as bisphenol-A (BPA). By exposing renewable, human, high-risk donor, breast epithelial cells (HRBECs) to BPA at concentrations that are detectable in human blood, placenta, and milk, we previously identified gene expression profile changes associated with activation of mammalian target of rapamycin (mTOR) pathway genesets likely to trigger prosurvival changes in human breast cells. We now provide functional validation of mTOR activation using pair wise comparisons of 16 independent HRBEC samples with and without BPA exposure. We demonstrate induction of key genes and proteins in the PI3K-mTOR pathway – AKT1, RPS6 and 4EBP1, and a concurrent reduction in the tumor suppressor, PTEN protein. Altered regulation of mTOR pathway proteins in BPA-treated HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor. Moreover, HRBECs pretreated with BPA, or the XE, methylparaben (MP), surmounted antiestrogenic effects of tamoxifen showing dose-dependent apoptosis evasion and induction of cell cycling. Overall, XEs, when tested in benign breast cells from multiple human subjects, consistently initiated specific functional changes of the kind that are attributed to malignant onset in breast tissue. Our observations demonstrate the feasibility of studying renewable human samples as surrogates and reinforce the concern that BPA and MP, at low concentrations detected in humans, can have adverse health consequences.
