美國(guó)的一項(xiàng)新研究發(fā)現(xiàn),，已被禁止用于嬰兒奶瓶的雙酚A和常用于化妝品防腐劑的羥苯甲酯會(huì)干擾乳腺癌藥物的治療效果,。
位于舊金山的加利福尼亞州太平洋醫(yī)學(xué)中心的研究人員發(fā)現(xiàn),，從乳腺癌高?；颊唧w內(nèi)提取的乳腺細(xì)胞在實(shí)驗(yàn)室中與雙酚A和羥苯甲酯接觸后,，便可能變得有能力對(duì)抗乳腺癌治療藥物,。該研究成果已發(fā)表在英國(guó)學(xué)術(shù)期刊《致癌作用》（Carcinogenesis）網(wǎng)絡(luò)版上,。
這項(xiàng)研究的負(fù)責(zé)人古德森介紹說(shuō),，他莫西芬是目前治療女性乳腺癌的標(biāo)準(zhǔn)藥物，也是男性乳腺癌治療使用最多的藥物,，可以減慢正常及癌變?nèi)橄偌?xì)胞的生長(zhǎng),，最終導(dǎo)致細(xì)胞死亡。然而被上述兩種化學(xué)物質(zhì)污染的乳腺細(xì)胞在他莫西芬面前顯得異常“驍勇善戰(zhàn)”,，沒(méi)有死亡而是持續(xù)生長(zhǎng),。
這一發(fā)現(xiàn)再次為雙酚A及羥苯甲酯的危害提供了證據(jù)。雙酚A被廣泛用于食品容器,、家用電器和購(gòu)物收據(jù)用紙中,。羥苯甲酯雖然不為公眾所熟知,，卻被廣泛用作化妝品等個(gè)人護(hù)理產(chǎn)品的防腐劑，美國(guó)食品和藥物管理局目前認(rèn)為羥苯甲酯對(duì)公眾健康沒(méi)有威脅,。
古德森表示,，雙酚A和羥苯甲酯由于應(yīng)用廣泛，人們?cè)谌粘Ｉ钪泻茈y避免接觸,。它們都具有類(lèi)激素作用,，有可能模擬雌激素對(duì)機(jī)體的危害，甚至比自然激素更難對(duì)付,。太平洋醫(yī)學(xué)中心的研究人員尚不清楚這兩種物質(zhì)對(duì)人體的影響是否可逆,，但認(rèn)為管理部門(mén)應(yīng)當(dāng)要求減少對(duì)它們的使用。（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.
