Development of a single DNA adduct-caused gene mutation assay as a model of low-dose exposure
| Project/Area Number |
22710068
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
YASUI Manabu 国立医薬品食品衛生研究所, 変異遺伝部, 主任研究員 (50435707)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | トキシコロジー / DNA 付加体 / 閾値 / 放射線 / 遺伝毒性発がん物質 / 環境 / DNA付加体 / 遺伝子変異 / ターゲティング |
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| Research Abstract |
Conventional technique of investigating an influence of low-dose exposure, commonly extrapolated from high-dose to low-dose region in Toxicology, is limited. Then, we have developed a new experimental system as a model of low-dose exposure, which can be used to determine the mutagenicity of synthetic DNA adducts at exon5 of thymidine kinase gene in human lymphoblastoid TSCER122 cells, derived from TK6 cell line. As a result, when an adduct forms at least one molecule on genomic DNA, it can cause gene mutation. The observation supports the idea that genotoxic carcinogens have no thresholds for the cancer risk. However, DNA repair functions in this experimental system do not work properly. In order to confirm the existence of threshold, it is necessary to study in detail the mechanisms of a single DNA adduct-caused gene mutation using TSCER122 cells knocked out DNA repair genes.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct,catalysed by human DNA polymerases2013
Author(s)
Sassa A, Kamoshita N, Matsuda T, Ishii Y,Kuraoka I, Nohmi T, Ohta T, Honma M, and Yasui M
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Journal Title
Mutagenesis
Volume: 28
Pages: 81-88
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[Presentation] gpt delta トランスジェニックラットを用いたライフステージ(週齢)を考慮したアクリルアミドの遺伝毒性評価2011
Author(s)
小山直己,安井学,木村葵,高見成昭, 鈴木拓也,増村健一,能美健彦,増田修 一,木苗直秀,松田知成,今井俊夫,本 間正充
Organizer
第38回日本トキシコロジー学会学術年会
Place of Presentation
横浜市
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