摘要
多污染物引发的联合毒性是环境污染物风险评价中的重要问题之一,然而此类研究相对不足.多溴联苯醚和重金属镉可在多种环境介质中共存,虽对其各自单独暴露所产生的毒性已有相对明确的认识,但对二者联合毒性效应及其分子机制的探索仍十分有限.生物信息学的发展为污染物的健康效应研究提供了一种新的思路.为此,本研究基于比较毒理基因组学数据库(CTD)分析了十溴联苯醚和镉在单独或共同暴露下所影响的基因和相关疾病,推测两种污染物对胎儿红系造血过程产生的潜在影响,并进一步整合外源红系细胞基因表达数据库中的基因芯片确证二者共同影响的基因集合.同时,通过对这些基因集合进行生物学过程和信号通路富集分析,筛选出潜在的靶基因JAK3和AKT2,并在无显著细胞毒性的暴露条件下,通过体外细胞实验验证了十溴联苯醚和镉对这两个靶基因表达的干扰.本研究结果可为预防多溴联苯醚和重金属的联合暴露风险提供一定的科学依据,同时,CTD数据库和外源特定疾病发生发展相关基因表达数据库联合使用,并结合传统毒理学研究手段的评价模式,可为污染物的共同暴露与特定疾病的相关性及分子机理的探索在研究思路和技术手段上提供参考.
Joint toxicity caused by co-existing pollutants is one of the issues in risk assessment of environmental pollutants. However, most studies still focus on the exposure to a single pollutant. Polybrominated diphenyl ethers (PBDEs) and heavy metal cadmium coexist under various environmental conditions. Although the toxicity caused by the single exposure to PBDEs or cadmium has been clarified, the understanding on their combined toxic effects and the corresponding molecular mechanisms still lack. To date, the rapidly developed bioinformatics provides a new potential approach for investigating the health effects of pollutants;yet such studies are limited. In the current study, we firstly analyzed the genes and diseases affected by the single or joint exposure to Decabrominated diphenyl ether (PBDE-209) and cadmium. In particular, we predicted the possible effects of the exposure to these two pollutants on erythropoiesis process at fetal stage by employing the Comparative Toxicogenomics Database (CTD). Then, the data derived from the ErythroDB, a public database of erythroid gene expression, were integrated to explore erythroid genes affected by the exposure to PBDE-209 and cadmium. Two target genes, JAK3 and AKT2, were screened out through enrichment analysis of biological process and signaling pathway. Finally, the results from in vitro experiments verified that PBDE-209 and cadmium can interfere erythroid differentiation of fetal liver through regulating the expression of JAK3 and AKT2 without inducing significant cytotoxicity. Our results may help prevent the combined exposure risk of PBDEs and heavy metals. Furthermore, our study provides a new pipeline for investigating the joint toxicity of pollutants with the incorporation of CTD database and the specific database of gene expression as well as the traditional toxicological approaches.
作者
王立新
王英雪
郑苗苗
崔建升
李珊
黄飞宇
WANG Lixin;WANG Yingxue;ZHENG Miaomiao;CUI Jiansheng;LI Shan;HUANG Feiyu(Pollution Prevention Biotechnology Laboratory of Hebei Province, College of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018;Hebei Key Laboratory of Molecular Chemistry for Drug, Shijiazhuang 050018)
出处
《环境科学学报》
CAS
CSCD
北大核心
2019年第6期2013-2023,共11页
Acta Scientiae Circumstantiae
基金
国家自然科学基金(No.201407040)
河北省自然科学基金(No.B2015208113)
河北省高等学校青年拔尖儿人才项目(No.BJ2019033)
关键词
十溴联苯醚
镉
比较毒理基因组学数据库
联合毒性
红系造血
decabromobiphenyl ether
cadmium
the comparative toxicogenomics database
combined exposure
erythropoiesis process
