Epigenetic mutation induced by environmental factors: a molecular mechanism elucidation of the DOHaD
| Project/Area Number |
23310044
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OHSAKO Seiichiroh 東京大学, 医学(系)研究科(研究院), 准教授 (00274837)
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| Co-Investigator(Kenkyū-buntansha) |
TOSHIYUKI Saito 国立研究開発法人放射線医学総合研究所, 重粒子医学センター, 主任研究員 (90205667)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKEDA Makio 一般財団法人残留農薬研究所, 毒性部, 室長
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Keywords | エピジェネティクス / 化学物質 / DOHaD / 環境汚染物質 / ダイオキシン / メチル化 / 発がん / P450 |
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| Outline of Final Research Achievements |
An attempt of elucidation of molecular mechanism of the DOHaD in which fetal environmental factors are hypothesized to cause an epigenomic alteration and memory persisted in adulthood. Additionally we developed a new genome-wide methylation analysis (MSD-AFLP method). The Cyp1a1 promoter of the liver is hypomethylated from day 3 after birth when given TCDD to pregnant mice and the altered methylation level is maintained until after maturity. Because the Dnmt3b dissociation was found by ChIP assay, we assumed mechanistic possibility of passive demethylation. Whereas we tested whether this memory could happen in the adulthood. In the mouse liver of 10 weeks of age, it was found that hypomethylation was caused by the early point in time such as 24 hours after TCDD administration, suggesting that active demethylation should be considered.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human neural progenitor cells: a combined study of metabolomics and morphological analysis2012
Author(s)
Qin XY, Akanuma H, Wei F, Nagano R, Zeng Q, Imanishi S, Ohsako S, Yoshinaga J, Yonemoto J, Tanokura M, Sone H
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Journal Title
Neurotoxicology
Volume: 33
Issue: 5
Pages: 1375-1380
DOI
Related Report
Peer Reviewed
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[Presentation] Establishment of a unique profiling method for DNA methylation frequency and its application to toxicology.2014
Author(s)
Aiba Toshiki, Saito Toshiyuki, Hayashi Akiko, Sato Shinji, Yunokawa Harunobu, Kurita Hisaka, Maruyama Toru, Fujibuchi Wataru, Tohyama Chiharu, Ohsako Seiichiroh
Organizer
SOT2014
Place of Presentation
Phoenix, Arizona (U.S.A.)
Year and Date
2014-03-27
Related Report
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