| Project/Area Number |
17K00555
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | Yokohama City University |
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Principal Investigator |
Kanaly Robert 横浜市立大学, 理学部, 教授 (00448656)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | DNA adductomics / RNA adductomics / DNA damage / 1,2-Naphthoquinone / Arylamines / Adductomics / アダクトーム / DNAダメージ / 培養細胞 / 質量分析 |
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| Outline of Final Research Achievements |
DNA and DNA/RNA adduct screening pipelines were constructed to conduct triple quadrupole mass spectrometry comparative adductomics by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI(+)-MS/MS) utilizing human cell lines that were exposed to hazardous aromatic chemicals. Nucleic acid adductomics approaches were combined with high resolution-(HR-MS) and NMR analyses to detect and to identify adducts of the naturally-occurring food constituent, safrole, the environmental pollutant, benzo[a]pyrene, the air pollutant, 1,2-naphthoquinone, and the arylhydroxylamine, N-(2,6-dimethylphenyl)hydroxylamine. The chemical structures of novel and known adducts and their mechanisms of formation were proposed and a new methodology for verification of DNA adductomics results to eliminate false positive annotations when it is applied as a DNA damage/genotoxicity screening test was developed and demonstrated by utilization of both DNA and RNA adductomics pipelines.
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| Academic Significance and Societal Importance of the Research Achievements |
Results of this work contributed to the advancement of the fields of nucleic acid adductomics and DNA damage research with applicability to human exposure and drug development. A new methodology, DNA/RNA adductomics was designed, tested and its proof-of-concept was demonstrated for the first time.
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