Evaluation of Species Difference of Adverse Health Effect due to Trichloroethylene utilizing DNA chip.

三氯乙烯（TCE）暴露于人肝细胞的方法与小鼠或大鼠肝细胞相同。我们正在做实验，关注肝细胞的状况。我们有时会遇到细胞状况的困难，如粘连不良。在这种情况下，我们不得不中断实验。根据贝叶斯定理选择处理后基因发生显著变化的探针。贝叶斯定理需要四个独立的实验。但由于上述情况，总数仍为3人。因此，我们通过方差分析临时选择了显著变化的探针。选取164个探针和141个探针，分别处理4小时和24小时。通过免费分析软件MAPPFinder对变化明显的探针进行功能分析。由于TCE是一种非基因毒性致癌物，因此生存信号或细胞凋亡尤其值得关注。在4小时的处理中，分析显示TRIM38的增加和VAPA的抑制。这两个基因是nf - κ b的诱导剂。还观察到TNFRSF10B的抑制和OPA1的诱导。前者是TNF超家族成员TRAIL的膜受体，与细胞凋亡的外源性通路有关。后者与线粒体的融合和裂变有关。OPA1的siRNA诱导细胞凋亡，该分子被认为是一种抗凋亡因子。本研究的目的是判断人类对TCE的反应是否接近小鼠或大鼠。我们认为，比起在数学上区分小鼠和大鼠的基因，更合理的判断是基于基因通过生物功能识别物种差异。我们参考了1500mg /kg连续口服给药实验。通过基因本体（Gene Ontology）或通路分析（pathway analysis）的功能分析，我们发现了表现出物种特异性反应和共同诱导的基因，抑制tgf - β信号转导是小鼠特异性的，诱导脂肪酸代谢相关基因在小鼠中更强。与补体和凝血相关的基因抑制被认为是常见的反应。少

Exposure of trichloroethylene (TCE) to human hepatocytes was done in the same way as that to mouse or rat hepatocytes. We are doing experiments, paying attention to the condition of hepatocytes. We sometimes have difficulties in the cell condition such as bad adhesion. We are forced to interrupt the experiment in such a case. Significantly changed probes of the gene by the treatment will be selected by Bayes' theorem. Bayes' theorem requires four independent experiments. Total number, however, remains three due to circumstances mentioned above. Thus, we temporary selected significantly changed probes by ANOVA. One hundred sixty four probes and one hundred forty one probes were selected for 4 hr and 24 hr treatment, respectively. Functional analysis was done for significantly changed probes by a free analysis soft wear MAPPFinder. Because TCE is a non-genotoxic carcinogen, survival signal or apoptosis is especially a matter of interest. In the 4 hr treatment, the analysis revealed induc … More tion of TRIM38 and suppression of VAPA. These two genes are inducer of NF-kappaB. Suppression of TNFRSF10B and induction of OPA1 were also observed. The former is a membrane receptor of TRAIL, a member of TNF superfamily, and related with extrinsic pathway of apoptosis. The latter is related with fusion and fission of mitochondrion. siRNA of OPA1 induced apoptosis and this molecule is implicated as an anti-apoptotic factor.The aim of the study is to judge weather human is close to mouse or rat with regard to response to TCE. We are thinking that it is reasonable to judge this based on genes identify species difference by biological function rather than genes mathematically discern mouse and rat. We referred to the consecutive 1500 mg/kg oral administration experiment for this matter. By functional analysis using Gene Ontology or pathway analysis, we identified genes that showed species specific response and were commonly induced Inhibition of TGF-beta signal transduction is specific to mouse and induction of genes related with fatty acid metabolism is stronger in mouse. Suppression of genes related with complement and coagulation is identified as common response. Less