Epigenetic Assessment of Environmental Chemicals Detected in Maternal Peripheral and Cord Blood Samples
Epigenetic Assessment of Environmental Chemicals Detected in Maternal Peripheral and Cord Blood Samples
复制标题
DOI：
10.1262/jrd.11-034a
复制
发表时间：
2011-08-01
影响因子：
1.8
通讯作者：
Shiota, Kunio
中科院分区：
文献类型：
--
作者：
Arai, Yoshikazu;Ohgane, Jun;Shiota, Kunio
表观遗传改变是化学物质对基因功能的长期影响下的一种新兴范式。在人类胎儿环境中检测到了各种化学物质，包括有机磷杀虫剂和重金属。表观遗传学通过DNA甲基化和组蛋白修饰，通过动态染色质重塑，是基因组稳定和基因功能的一种机制。为了研究这些环境化学物质是否可能导致表观遗传改变，我们研究了选定的化学物质对小鼠ES细胞(ESCs)异染色质形态变化和DNA甲基化状态的影响。通过4‘，6-二氨基-2-苯吲哚(DAPI)染色的异染色质监测，研究了有机磷杀虫剂、重金属及其代谢物等25种化学物质对小鼠胚胎干细胞表观遗传状态的影响。在接触这些化学物质48或96小时后，以脐带血的血清浓度对细胞进行观察。对表观致突变剂的候选基因区域的DNA甲基化的影响进行了检测。在这25种化学物质中，有5种化学物质(磷酸二乙酯(DEP)、汞(Hg)、可替宁(Cotinine)、硒(Se)和八氯二丙醚(S-421))引起了核染色的变化，表明它们影响了异染色质的条件。汞和硒引起基因座DNA甲基化异常。此外，0.1 ppb的DEP可引起ESCs不可逆的异染色质改变，DEP-、Hg-和S-421暴露的细胞也表现出类胚体(EB)形成障碍，这是一种早期胚胎的体外模型。我们建立了一个评估表观遗传诱变剂的系统。我们确定了可能对人类胎儿表观遗传状态产生影响的环境化学物质。
Epigenetic alteration is an emerging paradigm underlying the long-term effects of chemicals on gene functions. Various chemicals, including organophosphate insecticides and heavy metals, have been detected in the human fetal environment. Epigenetics by DNA methylation and histone modifications, through dynamic chromatin remodeling, is a mechanism for genome stability and gene functions. To investigate whether such environmental chemicals may cause epigenetic alterations, we studied the effects of selected chemicals on morphological changes in heterochromatin and DNA methylation status in mouse ES cells (ESCs). Twenty-five chemicals, including organophosphate insecticides, heavy metals and their metabolites, were assessed for their effect on the epigenetic status of mouse ESCs by monitoring heterochromatin stained with 4',6-diamino-2-phenylindole (DAPI). The cells were surveyed after 48 or 96 h of exposure to the chemicals at the serum concentrations of cord blood. The candidates for epigenetic mutagens were examined for the effect on DNA methylation at genic regions. Of the 25 chemicals, five chemicals (diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se) and octachlorodipropyl ether (S-421)) caused alterations in nuclear staining, suggesting that they affected heterochromatin conditions. Hg and Se caused aberrant DNA methylation at gene loci. Furthermore, DEP at 0.1 ppb caused irreversible heterochromatin changes in ESCs, and DEP-, Hg- and S-421-exposed cells also exhibited impaired formation of the embryoid body (EB), which is an in vitro model for early embryos. We established a system for assessment of epigenetic mutagens. We identified environmental chemicals that could have effects on the human fetus epigenetic status.