| Project/Area Number |
22241016
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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 | 一般 |
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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 |
NOHMI Takehiko 国立医薬品食品衛生研究所, 安全性生物試験研究センター, 客員研究員 (30150890)
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| Co-Investigator(Kenkyū-buntansha) |
MASUMURA Kenichi 国立医薬品食品衛生研究所, 変異遺伝部, 室長 (40291116)
YASUI Manabu 国立医薬品食品衛生研究所, 変異遺伝部, 主任研究官 (50435707)
SAJI Tetsuya (SUZUKI Tetsuya) 労働安全衛生総合研究所, 健康障害予防研究部, 研究員 (20573950)
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| Co-Investigator(Renkei-kenkyūsha) |
TOYODA Naomi (HOKAIWADO Naomi) 国立医薬品食品衛生研究所, 変異遺伝部, 非常勤職員 (70381853)
GRUZ Petr 国立医薬品食品衛生研究所, 変異遺伝部, 主任研究官 (10321853)
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| Project Period (FY) |
2010-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2011: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2010: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
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| Keywords | 閾値 / 遺伝毒性発がん物質 / トランスリージョンDNA合成 / DNAポリメラーゼζ / 突然変異 / DNA損傷 |
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| Research Abstract |
In regulatory toxicology, it is an axiom that there is no threshold for the action of genotoxic chemicals. Thus, genotoxic agents are not allowed to be present in food additives and others even at very low concentrations. However, humans possess various self defense mechanisms, which may suppress genotoxicity of chemicals at low doses. It is expected that self-defense mechanisms may constitute practical threshold for genotoxicity. In this study, we examined the possibility whether DNA polymerase zeta involved in translesion DNA synthesis plays a role in the practical threshold. To this end, we engineered human cells that expressed genetically modified DNA polymerase zeta. The cells expressing a variant of DNA polymerase zeta with low activity exhibited much higher sensitivity to oxidative genotoxic agents than the wild-type cells. We concluded that DNA polymerase zeta is an important constituent of the practical threshold for genotoxicity.
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