2013 Fiscal Year Final Research Report
Activation Mechanism of N-Nitrosodialkylamine by Reactive Oxygen Species
| Project/Area Number |
23590152
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INAMI Keiko 東京理科大学, 薬学部, 講師 (00271247)
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| Project Period (FY) |
2011 – 2013
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| Keywords | ニトロソジアルキルアミン / 活性酸素 / 代謝活性化 / フェントン試薬 / 酸化 / 発がん |
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| Research Abstract |
Carcinogenic and mutagenic N-nitroso compounds exist in our environment and can be formed in human body. To elucidate the new activation mechanism of N-nitrosodialkylamines by reactive oxygen species, the reaction mixture with N-nitroso-N-methylpropylamine and Fe2+-Cu2+-H2O2-NO was fractionated, and a direct-acting mutagen which has a ring structure was isolated. It is indicated that N-nitrosodialkylamines was activated by reactive oxygen species via new mechanisms.
Moreover, to clarify the structure-activity relationship for the mutagenesis of the mutagen X derived from N-nitroso-N-methylbutylamine with Fe2+-Cu2+-H2O2-NO, pyrazoline analogues were synthesized and assayed for their mutagenicity in Salmonella typhimurium TA1535. The data showed that the position of N-oxidation in the pyrazoline also affected on the mutagenic activity.
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