| Project/Area Number |
11672228
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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 | Okayama University |
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Principal Investigator |
KOBAYASHI-ARIMOTO Sakae OKAYAMA UNIVERSITY, FACULTY OF PHARMACEUTICAL SCIENCES, RESEARCH ASSOCIATE, 薬学部, 助手 (90212654)
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| Co-Investigator(Kenkyū-buntansha) |
NEGISHI Tomoe OKAYAMA UNIVERSITY, FACULTY OF PHARMACEUTICAL SCIENCES, ASSOCIATE PROFESSOR, 薬学部, 助教授 (80116491)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | NITROSOPROLINE / ULTRAVIOLET-A / MUTATION / DNA BREAKAGE / NITRIC OXIDE / ACTIVE OXYGEN / 8-OXODEOXYGUANOSINE / PHOTO TOXICITY / ニトロソ化アミノ酸 / 変異原性 / 太陽光 / 酸化的DNA傷害 / ヒト由来細胞 / ニトロソ化 / 遺伝子損傷 / DNA傷害 |
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| Research Abstract |
N-Nitrosoproline (NPRO) is endogenously formed from proline and nitrite. NPRO has been reported to be nonmutagenic and noncarcinogenic. In this study, we have detected the direct mutagenicity of NPRO plus natural sunlight towards S. typhimurium. Furthermore, formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a mutagenic lesion, was observed in calf thymus DNA treated with NPRO plus simulated sunlight. The treatment with NPRO and sunlight induced single strand breaks in the superhelical replicative form of phage M13mp2 DNA. Single strand DNA-breaks also occurred in the human fibroblast cells on treatment with NPRO plus UVA, as detected by the comet assay. An analysis using scavengers suggested that both reactive oxygen species and NO radical mediate the strand breaks. The formation of nitric oxide was observed in NPRO solution irradiated with UVA. We analyzed the photodynamic spectrum of mutation induction and DNA breakage using monochromatic radiation at a series of wavelengths between 300 nm and 400 nm. Both mutation frequencies and DNA breakage were highest at the absorption maximum of NPRO, 340 nm. The co-mutagenic and co-toxic actions of NPRO and sunlight merit attention as possible mechanisms increasing the carcinogenic risk from UVA irradiation.
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