Novel metabolic pathway for activation of carcinogenic N-nitroso compounds by reactive oxygen species
| Project/Area Number |
15590113
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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 | Kyoritsu University of Pharmacy |
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Principal Investigator |
MOCHIZUKI Masataka Kyoritsu University of Pharmacy, Professor, 薬学部, 教授 (10072414)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Satoko Kyoritsu University of Pharmacy, Research Associate, 薬学部, 助手 (70223518)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | N-nitrosodialkylamines / Fenton reagent / reactive oxygen species / mutagenicity / metabolic activation / ヒドロキシラジカル / 突然変異原生 / DNA損傷 |
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| Research Abstract |
N-Nitrosodialkylamines are metabolized by cytochrome P450, and formed alkyldiazonium ions through α-hydroxylnitrosamines, and then finally showed mutagenicity and carcinogenicity. However, the precise process of their activation is less well understood. N-Nitrosodialkylamines were treated with hydroxyl radical generating system, ferrous ion-cupric ion-hydrogen peroxide system (defined as modified Fenton reagent), and mutagens formed in this system were identified in order to investigate a novel metabolic pathway of N-nitroso compounds.
N-Nitroso-N-methylbutylamine (NMB) showed mutagenicity after treatment with modified Fenton reagent. We already reported that 5-methyl-5-nitro-1-pyrazoline 1-oxide (mutagenX) as a novel mutagen identified from the reaction mixture of NMB and modified Fenton reagent. Mutagen X was synthesized and tested the mutagenicity. Furthermore, mutagen X in the reaction mixture was quantified, and then compared the mutagenicities among the reaction mixture and mutagen X alone. The mutagenicity of reaction mixture was higher than that of mutagen X alone by a factor of 15. The result showed that there are possibilities of other stronger mutagen formed or of enhancement of the mutagenicity by other products in the reaction mixture. In this study, we isolated another mutagen, showed higher mutagenicity than mutagen X, from the reaction mixture of NMB and modified Fenton reagent.
Further research is necessary to identify the novel metabolite and elucidate the mechanism of its formation in the reaction mixture of N-nitroso compounds treated with reactive oxygen species.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Electron-transfer mechanism in radical-scavenging reactions by a vitamin E model in a protic medium.2005
Author(s)
Nakanishi I, Kawashima T, Ohkubo K, Kanazawa H, Inami K, Mochizuki M, Fukuhara K, Okuda H, Ozawa T, Itoh S, Fukuzumi S, Ikota N.
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Journal Title
Org Biomol Chem 3
Pages: 626-629
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Kinetic study of the electron-transfer oxidation of the phenolate anion of a vitamin E model by molecular oxygen generating superoxide anion in an aprotic medium.2003
Author(s)
Nakanishi I, Miyazaki K, Shimada T, Iizuka Y, Inami K, Mochizuki M, Urano S, Okuda H, Ozawa T, Fukuzumi S, Ikota N, Fukuhara K.
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Journal Title
Org Biomol Chem 1
Pages: 4085-4088
Description
「研究成果報告書概要(和文)」より
Related Report
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