Application of oligonucleotide microarray technology to toxic occupational exposures
Application of oligonucleotide microarray technology to toxic occupational exposures
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DOI：
10.1080/15287390701738509
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发表时间：
2008-01-01
影响因子：
2.6
通讯作者：
Weston, Ainsley
中科院分区：
文献类型：
--
作者：
Gwinn, Maureen R.;Weston, Ainsley
微阵列技术在分析生物系统中的有毒职业暴露方面取得了进展。即使没有确定特定的基因或途径，微阵列分析也是寻找暴露的生物标记物的理想方法。现在可以同时对数千个基因进行分析，而不是像过去那样只对少数基因进行分析。这一能力已被用于在动物模型中分析各种职业毒素的基因表达谱，以根据反应将毒素分类为特定类别。对正常人类细胞株的分析允许这种分析的扩展，以调查个体间变异在对各种毒素的反应中所起的作用。该方法被用来分析我们实验室中四种与职业相关的毒素：喹恶啉农药氧硫喹(OTQ)；有机磷农药马拉硫磷；个人护理和化妆品中常见的化学物质邻苯二甲酸二丁酯(DBP)；以及环境和职业致癌物质苯并[a]芘(BaP)。每一次暴露的结果突出了与这些职业暴露相关的信号通路。这两种杀虫剂都显示出代谢酶的增加，而DBP则显示出与生育相关的基因变化。暴露于BaP后，与致癌性相关的两种细胞色素P450发生了改变。当与职业暴露信息一起使用时，这些数据可用于加强风险评估，使工作场所对更大比例的劳动力更安全，包括易受暴露相关疾病影响的个人。
Microarray technology has advanced toward analysis of toxic occupational exposures in biological systems. Microarray analysis is an ideal way to search for biomarkers of exposure, even if no specific gene or pathway has been identified. Analysis may now be performed on thousands of genes simultaneously, as opposed to small numbers of genes as in the past. This ability has been put to use to analyze gene expression profiles of a variety of occupational toxins in animal models to classify toxins into specific categories based on response. Analysis of normal human cell strains allows an extension of this analysis to investigate the role of interindividual variation in response to various toxins. This methodology was used to analyze four occupationally related toxins in our lab: oxythioquinox (OTQ), a quinoxaline pesticide; malathion, an organophosphate pesticide; di-n-butyl phthalate (DBP), a chemical commonly found in personal care and cosmetic items; and benzo[a]pyrene (BaP), an environmental and occupational carcinogen. The results for each exposure highlighted signaling pathways involved in response to these occupational exposures. Both pesticides showed increase in metabolic enzymes, while DBP showed alterations in genes related to fertility. BaP exposure showed alterations in two cytochrome P450s related to carcinogenicity. When used with occupational exposure information, these data may be used to augment risk assessment to make the workplace safer for a greater proportion of the workforce, including individuals susceptible to disease related to exposures.