2007 Fiscal Year Final Research Report Summary
Evaluation of species difference in extrapolation of animal toxicogenomic data to human
| 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 Keio University, School of Medicine, Instructor (20338023)
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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)
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| Project Period (FY) |
2006 – 2007
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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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[Presentation] The study of discerning species difference between human, mouse and rat by transcriptome of primary hepatocytes exposed to trichloroethylene2007
Author(s)
Nakashima, H, Sano, Y, Yoshioka, N, Eton, N, Takebayashi, T, Omae, K
Organizer
14th annual meeting of Human and Animal Bridging Research Organization
Place of Presentation
Tokyo
Year and Date
2007-05-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Species Difference of human, mouse and rat transcriptome of primary hepatocytes exposed to trichloroethylene2007
Author(s)
Nakashima, H, Sano, Y, Yoshioka, N, Etoh, N, Takebayashi, T, Omae, K
Organizer
77th annual meeting of Japan Hygiene Society
Place of Presentation
Osaka
Year and Date
2007-03-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The evaluation of species difference caused by trichloroethylene. -The association between gene expression profile and pathological findings-2007
Author(s)
Sane, Y, Yoshioka, N, Nakashima, H, Etoh, N, Nishiwaki, Y, Takebayashi, T, Omae, K
Organizer
77th annual meeting of Japan Hygiene Society
Place of Presentation
Osaka
Year and Date
2007-03-28
Description
「研究成果報告書概要(欧文)」より
