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

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.

人类可通过食物、饮水与空气接触各类化学物质，其中相当一部分可模拟内源性激素的生理作用。其中一类典型化学物质为双酚A（Bisphenol A，BPA），作为合成化学物，已有研究证实其可导致啮齿类动物模型出现发育异常，并增加乳腺癌易感风险。与之相对，植物化学物染料木黄酮（genistein）据报道可抑制啮齿类动物体内化学物质诱导的乳腺癌；此外，日常食用富含大豆染料木黄酮饮食的亚洲人群，其乳腺癌与前列腺癌的发病率更低。
本研究旨在达成两大目标：（1）采用同位素串联质量标签定量质谱技术（Isobaric Tandem Mass Tags quantitative mass spectrometry，TMT-MS）结合多维蛋白质鉴定技术（Multidimensional Protein Identification Technology，MudPIT），从青春期前暴露于双酚A或染料木黄酮的大鼠血清中筛选易感性蛋白质生物标志物；（2）探究这些蛋白质与癌变进程的相关性。
青春期前暴露于双酚A与染料木黄酮后，大鼠血清在出生后第21天（postnatal day 21，PND 21）分别有63种与28种蛋白质的表达水平发生显著改变，而在出生后第35天（PND 35）则分别有9种与18种蛋白质表达水平出现变化。本研究证实了定量蛋白质组学技术在探究化学物质暴露对大鼠血清蛋白质组影响方面的应用价值，同时也表明该技术有望揭示双酚A与染料木黄酮所调控的、参与癌变过程的细胞靶点。