Classification of heavy-metal toxicity by human DNA microarray analysis
Classification of heavy-metal toxicity by human DNA microarray analysis
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DOI：
10.1021/es062717d
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发表时间：
2007-05-15
影响因子：
11.4
通讯作者：
Okabe, Satoshi
中科院分区：
文献类型：
--
作者：
Kawata, Koji;Yokoo, Hiroyuki;Okabe, Satoshi
微阵列技术被证明是一种有用的工具，可以对未定义的环境毒物进行分类，研究潜在的毒性机制，并通过检查假定毒物对基因表达谱的整体影响来识别候选毒物特异性遗传标记。本研究的目的是通过与众所周知的化学物质诱导的基因表达模式进行比较来评估六种重金属的毒性。为此，我们首先使用 DNA 微阵列鉴定了 HepG2 在 2,3-二甲氧基-1,4-萘醌 (DMNQ)、苯酚和 N-亚硝基二甲胺 (DMN) 暴露下发生特异性改变的基因，并选择这些基因作为模型化学品。根据这些基因的表达谱，评估了砷、镉、镍、锑、汞和铬六种重金属的毒性。特定的基因改变和层次聚类揭示了六种重金属的生物作用与DMNQ的生物作用明显相关，据报道DMNQ是一种产生活性氧（ROS）的化学物质，并诱导与细胞增殖反应相关的基因。这些结果表明，可能由ROS引起的细胞增殖反应是高剂量重金属的主要表观生物作用，支持了之前的报道。总体而言，通过 DNA 微阵列进行基于机制的分类将是评估环境样品毒性的有效方法。
Microarray technology is proving to be a useful tool to classify undefined environmental toxicants, to investigate underlying mechanisms of toxicity, and to identify candidate toxicant-specific genetic markers by examining global effects of putative toxicants on gene expression profiles. The aim of this study was to evaluate the toxicities of six heavy metals through the comparison with gene expression patterns induced by well-known chemicals. For this purpose, we first identified the genes altered specifically in HepG2 under the exposure of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), phenol, and N-nitrosodimethylamine (DMN), which were selected as the model chemicals, using DNA microarray. On the basis of the expression profiles of these genes, toxicities of six heavy metals, arsenic, cadmium, nickel, antimony, mercury, and chromium, were evaluated. The specific gene alteration and hierarchical clustering revealed that biological action of six heavy metals was clearly related to that of DMNQ which has been reported to be a reactive oxygen species (ROS) generating chemical and which induced the genes associated with cell proliferative responses. These results suggest that cell proliferative responses which are probably caused by ROS are a major apparent biological action of high-dose heavy metals, supporting the previous reports. Overall, a mechanism-based classification by DNA microarray would be an efficient method for evaluation of toxicities of environmental samples.