Effects of the pesticide thiuram: Genome-wide screening of indicator genes by yeast DNA microarray
Effects of the pesticide thiuram: Genome-wide screening of indicator genes by yeast DNA microarray
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DOI：
10.1021/es015705v
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发表时间：
2002-09-15
影响因子：
11.4
通讯作者：
Iwahashi, H
中科院分区：
文献类型：
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作者：
Kitagawa, E;Takahashi, J;Iwahashi, H
虽然已经有关于农药秋兰姆毒性的研究，但本研究是第一个尝试使用微阵列技术整合全基因组反应的研究。从DNA微阵列实验中发现，暴露于秋兰姆导致酵母细胞中基因表达的改变，并且参与解毒和应激反应的许多基因被高度诱导。根据MIPS酵母数据库对诱导基因进行分类。与折叠和蛋白水解有关的基因的诱导反映了秋兰姆处理的蛋白质变性和降解效应。参与氧化还原和防御反应氧的基因的诱导也表明秋兰姆还具有其他作用，例如氧化应激。碳水化合物代谢和能量基因也被高度诱导，这些基因产物可能起到为解毒机制提供能量的作用。此外，鉴于秋兰姆诱导参与DNA修复的一些基因，秋兰姆可能导致DNA损伤。因此，如以前的报告所述，秋兰姆是一种潜在的阳性有毒化学品。另一方面，基于DNA微阵列实验的结果选择YKL 071 W、YCR 102 C、YLR 303 W和YLL 057 C，并用于启动子活性测定。秋兰姆处理影响了这些基因的启动子，表明该技术可用于生物标志物候选物的选择。
Although there have been studies on the toxicity of the pesticide thiuram, the present study is the first one to attempt to integrate a whole genomic response using microarray technology. From the DNA microarray experiment, it was found that exposure to thiuram led to alterations of gene expression in yeast cells and that many genes involved in detoxification and stress response were highly induced. The induced genes were classified according to the MIPS yeast database. The induction of genes concerned with folding and proteolysis reflects the protein denaturing and degradation effects of the thiuram treatment. The induction of genes involved in redox and defense against reaction oxygen species also suggests that thiuram has other effects, such as oxidative stress. Genes classified for carbohydrate metabolism and energy were also highly induced, and these gene products may play the role of providing the energy for the detoxification mechanism. In addition, in view of the induction of some genes involved in DNA repair, thiuram potentially causes DNA damage. Therefore, as stated in previous reports, thiuram is a potential positive toxic chemical. On the other hand, YKL071W, YCR102C, YLR303W, and YLL057C were selected based on the result of a DNA microarray experiment and used for the promoter activity assay. Thiuram treatment affected the promoter of these genes, indicating that this technique could be used for the selection of biomarker candidates.