| Project/Area Number |
16510041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Institute for Environmental Sciences, University of Shizuoka |
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Principal Investigator |
IBUKI Yuko University of Shizuoka, Institute for Environmental Sciences, Associate Professor, 環境科学研究所, 准教授 (30236781)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Norio University of Shizuoka, Institute for Environmental Sciences, Professor, 環境科学研究所, 教授 (10169039)
NAITOH Hirotaka University of Shizuoka, Institute for Environmental Sciences, Associate Researcher, 環境科学研究所, 助教 (30254262)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | polycyclic aromatic hydrocarbons / ultraviolet A / DNA double strand breaks / histone / γ-H2AX / chromatin / cancer / histone H2AX / Ku-80 / 共焦点レーザー顕微鏡 / GFP |
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| Research Abstract |
In this study, we examined the mechanism of immune suppression after coexposure to polycyclic aromatic hydrocarbons (PAHs) and ultraviolet A (UVA). As the high cytotoxicity was considered one of the reasons for immune suppression after coexposure, we focused on clarification of the mechanism of cytotoxicity.
Benzo[a]pyrene (BaP) is one of the most commonly studied PAHs. Coexposure to BaP and UVA induced DNA double strand breaks (DSBs), which was confirmed by pulse-field gel electrophoresis and using DSBs repair enzyme-deficient cell line. Furthermore, phosphorylation of histone H2AX (γ-H2AX) which has been clarified to be generated at the sites of DSBs after exposure to ionizing radiation and antitumor agents, etc., was significantly increased after coexposure to BaP and UVA. γ-H2AX was detectable at low doses of BaP and UVA which had no cytotoxicity. Therefore, the detection of γ-H2AX is considered to be useful for sensitive detection of phototoxicty of environmental chemicals. In addition, the repair of DSBs was relative to γ-H2AX, suggesting that γ-H2AX after coexposure to PAHs and UVA was an important process to suppress the promotion of skin cancer.
This is the first study to evaluate the effects of environmental chemicals in the point of histone modification change. We are planning to construct new evaluation systems focused on other histone modification. In addition, the relationship between γ-H2AX and suppression of immune system after coexposure to PAHs and UVA is a future subject to be clarified.
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