Mechanism of DNA damaging by photo- and metabolic products of carcinogenic ethylbenzene
| Project/Area Number |
16590097
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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 |
Environmental pharmacy
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| Research Institution | Meijo University |
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Principal Investigator |
KOJIMA Nakao Meijo University, Faculty of Pharmacy, Professor, 薬学部, 教授 (80333178)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANISHI Shosuke Mie University, Department of Medicine, Professor, 医学部, 教授 (10025637)
HASHIZUME Kiyomatsu Meijo University, Faculty of Pharmacy, Assistant Professor, 薬学部, 助教授 (50076733)
TODA Chitose Meijo University, Faculty of Pharmacy, Assistant, 薬学部, 助手 (00076738)
UEDA Koji Meijo University, Faculty of Pharmacy, Assistant, 薬学部, 助手 (30351092)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Environmental chemicals / DNA damage / VOC / ROS / 8-oxodG / Structure-activity relationship / light irradiation / metabolic activation / 光照射 / 代謝活性化 / 化学発がん / 酸化的遺伝子損傷 / 酸化還元サイクル / 活性酸素種 / 光活性化 / エチルベンゼン / 光分解 / 肝ミクロソーム / P450 |
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| Research Abstract |
Ethylbenzene is an air pollutant detected often in the environment. Ethylbenzene is a non-mutagenic carcinogen and its carcinogenesis mechanism is not elucidated. In this research, we showed that ethylbenzene transformed into genotoxic by light exposure or metabolism. Its underlying mechanism involves peroxiethylbenzene and ethyl catechol/hydroquinone, which generates reactive oxygen species in their redox reaction with Cu and damages DNA especially at 5' of consecutive guanine. We expanded this mechanism to other several environmental chemicals that follows. 1)Nonylphenol, a government-certified endocrine disruptor turned to be genotoxic by light irradiation. 2)Methyl paraben, a widely used preservative, was activated by the combination of light and metabolism. 3)An additional functional group suppressed DNA damage of catechol. This structure-activity relationship is useful to predict the risk of chemicals. The key structure for DNA damaging activity is aromatic hydroxylation and this is important for other activities such as endocrine disruption. 4)Plasticizers revealed its potential estrogenic activity after sunlight exposure. 5)Sunscreens generated hydroxyl radical and activated themselves by sunlight irradiation. 6)A specific hydroxylation made flavonoides highly anti-estrogenic. As stated above, this study provided many important findings for risk assessment of environmental chemicals.
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Report
(3 results)
Research Products
(19 results)
