Establishment of practical epigenetic toxicity evaluation system using newly developed reporter mice
| Project/Area Number |
17H01882
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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 and chemicals
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大塚 まき 星薬科大学, 薬学部, 助手 (40734372)
山本 直樹 星薬科大学, 先端生命科学研究所, 特任助教 (50757432)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | エピジェネティクス / DNAメチル化 / 化学物質 / エピジェネティック毒性 / トキシコロジー / 新規レポーターマウス / ゲノム / 毒性試験 / レポーター / 有害化学物質 |
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| Outline of Final Research Achievements |
With the rise of molecular and cellular biology, the epigenetic effects of chemicals have begun to be recognized as a problem in the field of toxicology. We named such toxicity epigenetic toxicity and developed a reporter assay system that can easily detect epigenetic effects of chemicals by connecting luciferase gene and tdTomato gene as reporters downstream of two promoters. We selected azacytidine as a positive chemical and examined this system, and confirmed that azacytidine increased the reporter activity and actually decreased DNA methylation. It is expected that this system will be used as a screening system for various chemicals in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
エピジェネティック毒性は潜在的リスクとして認識されていますが、実際にエピジェネティック毒性を有することが報告されている化学物質は多くありません。その理由として、エピジェネティクスには高度な分子細胞生物学的手法が必要なためと考えられます。そのような手法は毒性試験を主とする研究現場には馴染みが薄く、その結果エピジェネティック毒性が検討されないままになっています。本研究で開発したアッセイ系は培養細胞に化学物質を処理し、溶解液中の酵素活性を測定するだけで済みます。これなら毒性試験の現場でも導入可能であり、今後エピジェネティック毒性検出に活用されることが期待されます。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Aberrant epigenetic gene regulation in hippocampal neurogenesis of mouse offspring following maternal exposure to 3,3’-iminodipropionitrile2019
Author(s)
Tanaka T, Nakajima K, Masubuchi Y, Ito Y, Kikuchi S, Ideta-Ohtsuka M, Woo GH, Yoshida T, Igarashi K, Shibutani M.
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Journal Title
The Journal of Toxicological Sciences
Volume: 44
Issue: 2
Pages: 93-105
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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[Journal Article] DNA Methylome Analysis Identifies Transcription Factor-Based Epigenomic Signatures of Multilineage Competence in Neural Stem/Progenitor Cells.2017
Author(s)
Sanosaka T, Imamura T, Hamazaki N, Chai M, Igarashi K, Ideta-Otsuka M, Miura F, Ito T, Fujii N, Ikeo K, Nakashima K
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Journal Title
Cell Rep
Volume: 20
Issue: 12
Pages: 2992-3003
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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