| Project/Area Number |
18590573
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Keio University |
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Principal Investigator |
SANO Yuri (2007) Keio University, School of Medicine, Instructor (20338023)
中島 宏 (2006) 慶應義塾大学, 医学部, 助手 (80217710)
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| Co-Investigator(Kenkyū-buntansha) |
OMAE Kazuyuki Keio University, School of Medicine, Professor (60118924)
YOSHIOKA Noriyuki Keio University, School of Medicine, Instructor (70365229)
ETOH Norihito Tokai University, School of High-Technology for Human Welfare, Assistant Professor (60365228)
佐野 有理 慶應義塾大学, 医学部, 助手 (20338023)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | trichloroethylene / species difference / DNA microarray / transcriptome / primary hepatncyte |
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| Research Abstract |
In 2006, we obtained the transcriptome of human hepatocytes exposed to trichloroethylene (TCE). Thus, we made inter-species comparison of human, mouse and rat transcriptome. With the Bayes' theorem, we extracted significantly changed probes(p<0.01) after filtering probes whose flag showed present or marginal in at least three out of four samples in each group. Analysis was conducted by the publicly available software such as MAPPFinder or GSEA (Gene Set Enrichment Analysis). The functional analysis by MAPPFinder revealed up-regulation of beta oxidation related genes only in mice treated 5mM TCE for 24 hours. The analogy of transcriptome was studied by GSEA. Down-regulated genes in TCE exposure were found to be similar to those of rats. Trichloroacetic acid and trichloroethanol are metabolites in human. Human is similar to mice in the view point of metabolism. Trichloroacetic acid and trichloroethanol are thought to be important for peroxisome proliferation, of which downstream beta oxidation lies. Given that beta oxidation is the beginning of carcinogenesis, the result of the functional analysis by MAPPFinder is interesting. Rodents are higher than humans in the sensitivity to peroxisome proliferators, and mice are higher than rats among rodents. Up-regulation of beta oxidation related genes in mice is in accordance with the results of carcinogenicity test, where TCE causes liver cancer preferentially in mice. DNA microarray, which is feasible to study numerous pathways in one experiment, was thought to be useful to evaluate human health risk of chemicals along with elucidation of toxicological mechanism by animals.
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