Study of Oxidative damages on guanine adducts and hunting of markers for damages on DNA by means of electrochemical methods
| Project/Area Number |
17590035
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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 |
Physical pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
ESAKA Yukihiro Gifu Pharmaceutical University, Pharmacy, Associate professor, 薬学部, 助教授 (70244530)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | oxidative damage / cyclic-propanoguanine / drinking / electrolytic oxidation / dimer / MS / NMR / Intra-strand linkage / サイクリックプロパノグアニン / アルコール摂取 / LC / ESI-MS / カルボカチオン / 分子計算 |
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| Research Abstract |
Some recent statistical studies in medicine suggest that DNA damages by acetaldehyde (AA) is one of initial actions in carcinogenesis occurred by drinking. Cyclic-propanoguanine (CPrG) will be the most expected candidate as a damaged form in DNA by AA. Based on the theory of electron-hopping along DNA chains through π-π stacking in an oxidative damaging process, I have investigated additional oxidations following the formation of CPrG on DNA as a part of a mis-reading mechanism of base sequences in DNA occurred by CPrG formation by AA.
Electrolytic oxidation of CPrG in aqueous media generated a unique dimer compound of CPrG as a major product. Detailed NMR studies indicated that the each CPrG parts had very similar but not same structure representing chemical shifts different a little from each other. Additionally, the linkage sites on each CPrG moieties decided to be certain different positions on CPrG. The expected structure of the dimer has been strongly supported by MS/MS data.
The identified structure can be formed by coupling between CPrG itself and a carbocation of CPrG that will be generated via elimination of both two electrons and a proton. This proposed reaction route has been supported by a MO calculation. Conformational studies with MOPAC suggest that the dimer can be formed with an intrastrand mannar and an interstrand manner in DNA and, particularly, the former manner can be attributable to the mis-reading of DNA information.
Quite recently I have performed electrolysis of treated DNA double strands (Calf thymus). including CPrG and have found the dimer structure in the treated DNA. The dimer may become an valuable biomarker indicating magnitude of risk of carcinogenesis for drinkers.
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Report
(3 results)
Research Products
(2 results)
