| Project/Area Number |
13357005
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Hygiene
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| Research Institution | University of Yamanashi (2003)
山梨医科大学 (2001-2002) |
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Principal Investigator |
MAEDA Shuichiro University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院・医学工学総合研究部, 教授 (10117244)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masayuki University of Tsukuba, Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Professor, 基礎医学系(先端学際領域研究センター), 教授 (50166823)
KOIZUMI Akio Kyoto University, Department of Health and Environmental Sciences, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (50124574)
NAKAJIMA Tamie Nagoya University, Department of Occupational and Environmental Health, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (10020794)
KAGAMI Yoshihiro Ecogenomics, Inc., Chief Research Scientist, 主席研究員・研究職
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥28,080,000 (Direct Cost: ¥21,600,000、Indirect Cost: ¥6,480,000)
Fiscal Year 2003: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2001: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
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| Keywords | toxic chemicals / genetically altered mice / bioassay system / toxicological assessment / dioxins / 環境リスク |
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| Research Abstract |
Currently, more than 100,000 chemicals have been used in industry. These chemicals have been released to the environment without any toxicological evaluation. To regulate these chemicals properly, the development of methods for toxicological assessment is required. Thus, we performed experiments to develop a repertoire of genetically altered mice for evaluating the toxicity of chemicals. The results of our experiments are as follows.
1)We established an extremely rapid, sensitive, easy, and specific assay for dioxin and dioxin like chemicals (Maeda, S.)
2)In the search for dioxin-responsive genes in the mouse fetal brain we used differential mRNA display and DNA microarray and found that secreted frizzled-related protein 2 and c-myc genes that encode a Wnt modulator and a Wnt target, respectively, were up-regulated by perinatal exposure of mice to dioxin (Maeda, S. & Kagami, Y.).
3)Nrf2-null mice were very sensitive to acetaminophane and very often suffered from acute hepatotoxicity (Yama
… More
moto, M.)
4)When AhRR, which was identified as a repressor of AhR, was deleted in mouse, the induction of AhR target genes were increased and prolonged (Yamamoto, M.).
5)We have conducted genetic analyses of individuals highly susceptible to goiter and found two linked regions on chromosome 3 and 4. We have sequenced solute carrier family genes, SLC26A1 and SLC2A9. The sequence, however, suggested that these two genes were not associated with familial goiter (Koizum, A.).
6)The role of peroxisome proliferators-activated receptor a (PPARa) in the di (2-ethylhexyl) phthalate (DEHP)-induced reduction of fertility, which was assessed by measuring the numbers of pups born and pups lived more than 16 weeks per breeding pair, was assessed using Sv/129 wild-type and PPARa-null mice. Our results suggested that the reduction of fertility without the maternal or paternal genital organ toxicity found in DEHP-exposed wild-type mice is partly caused by a signal triggering energy overconsumption via PPARa in the maternal body (Nakajima, T.). Less
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