Suppression of oxidative stress-induced DNA damage by natural coumarins
| Project/Area Number |
13660136
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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 |
食品科学・栄養科学
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
KANEKO Takao Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo. Metropolitan Institute of Gerontology, Redox Regulation Research Group, Senior Research Scientist, 東京都老人総合研究所・老化レドックス制御研究グループ, 主任研究員 (80100113)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Natural coumarins / Esculetin / Esculin / Oxidative DNA damage / Anti-carcinogenesis / Chemical carcinogen / クマリン化合物 / 細胞取込 / チコリー / 抗発癌 / 化学発癌剤 / 膵癌 / N-ニトロソビス(2-オキソプロピル)アミン / 大腸癌 / 1,2-ジメチルヒドラジン / 8-ヒドロキシ-2'-デオキシグアノシン |
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| Research Abstract |
Esculetin and esculin, the 6-glycoside of esculetin, are natural coumarins found in a variety of plant sources such as chicory and dandelion. Protective effects of coumarins against oxidative DNA damage induced by lipid peroxide (LOOH) and chemical carcinogens and carcinogenesis induced by chemical carcinogens were examined in cultured cells and animals. Treatment of cells with esculetin significantly suppressed the increase in 8-oxo-2'-deoxyguanosine (8-oxodG) content induced by LOOH and iron(III) ion. Pretreatment of cells with esculetin was effective in protecting cellular DNA against oxidative damage induced by subsequent treatment with LOOH and iron(III) ion. Pretreatment with esculin was also effective, but to a lesser extent. Since esculetin was detected in cells and culture medium after treatment with esculin, a sugar moiety in the esculin molecule appears to be hydrolyzed during treatment. Furthermore, effects of esculetin and esculin on 8-oxodG formation and carcinogenesis in
… More
duced by chemical carcinogens, N-nitrosobis(2-oxopropyl)amine (BOP) and 1,2-dimethylhydrazine (DMH), were examined in the pancreas of female Syrian golden hamsters and the colons of male Fischer 344 rats. Esculetin and esculin suppressed significantly the BOP-and DMH-induced increases in 8-oxodG contents in the target organs. The effect of esculin on pancreatic and colon carcinogenesis was also investigated by the rapid production models. The incidence of invasive tumors in the hamster pancreas given esculin during the initiation phase was significantly smaller than in the control group, while esculin given during the promotion phase showed no apparent effects. The ingestion of esculin during the initiation phase significantly reduced the incidence of multiplicity and of aberrant crypt foci (ACF), while the esculin treatment during the post-initiation phase decreased only the incidence of ACF. These results suggest that the intake of esculetin and esculin has an inhibitory effect on oxidative stress-induced DNA damage and carcinogenesis in the target organs. Less
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Report
(4 results)
Research Products
(13 results)
