Journal of Proteome Research, 2014, 13(3):1502-14.

Alterations in the Rat Serum Proteome Induced by Prepubertal Exposure to Bisphenol A and Genistein

Angela Betancourt, James A Mobley, Jun Wang, et al

Department of Pharmacology and Toxicology, University of Alabama at Birmingham (UAB) , 1670 University Boulevard, Volker Hall 241, Birmingham 35294, Alabama, United States

Humans are exposed to an array of chemicals via the food, drink and air, including a significant number that can mimic endogenous hormones. One such chemical is Bisphenol A (BPA), a synthetic chemical that has been shown to cause developmental alterations and to predispose for mammary cancer in rodent models. In contrast, the phytochemical genistein has been reported to suppress chemically induced mammary cancer in rodents, and Asians ingesting a diet high in soy containing genistein have lower incidence of breast and prostate cancers. In this study, we sought to: (1) identify protein biomarkers of susceptibility from blood sera of rats exposed prepubertally to BPA or genistein using Isobaric Tandem Mass Tags quantitative mass spectrometry (TMT-MS) combined with MudPIT technology and, (2) explore the relevance of these proteins to carcinogenesis. Prepubertal exposures to BPA and genistein resulted in altered expression of 63 and 28 proteins in rat sera at postnatal day (PND) 21, and of 9 and 18 proteins in sera at PND35, respectively. This study demonstrates the value of using quantitative proteomic techniques to explore the effect of chemical exposure on the rat serum proteome and its potential for unraveling cellular targets altered by BPA and genistein involved in carcinogenesis.

美国《蛋白质组研究杂志》，2014年3月

青春期前暴露于双酚 A 和金雀异黄素诱导的大鼠血清蛋白质的变化

安吉拉 贝当古，詹姆斯 A 莫布雷，王俊，等

美国阿拉巴马州阿拉巴马大学伯明翰分校药理学和毒理学学院

人类通过大量的食品、 饮料和空气接触到可以模仿内源激素的化学物质。这样一种化学物质是双酚 A (BPA)，一种已被证明在啮齿动物模型中会导致进程改变，使之更易患乳腺癌的合成化学试剂。与此相反的是，植物化学物质金雀异黄素被报道可以抑制啮齿类动物化学诱导的乳腺癌，并且摄入大量含有金雀异黄素大豆饮食的亚洲人患上乳腺癌和前列腺癌的发病率较低。在此研究中，我们发现: （1）使用定量质谱 (TMT-MS) 与 MudPIT 技术相结合的等压串联质量标记法，确认蛋白质生物标志物的敏感性从暴露于双酚 A 或金雀异黄素的大鼠血清中，和 （2） 探究这些蛋白质与癌变的相关性。青春期前接触双酚 A 和金雀异黄素分别导致大鼠血清中的蛋白质 63 和 28 在出生后第21天 (PND)改变，而血清蛋白质 9 和 18 在PND35改变。这项研究表明使用定量蛋白质组学技术探讨化学物质接触对大鼠血清蛋白质组的影响的价值以及其阐明双酚 A 和金雀异黄素改变癌变细胞靶向的潜力。