| Project/Area Number |
16H06306
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
廣田 耕志 東京都立大学, 理学研究科, 教授 (00342840)
笹沼 博之 京都大学, 医学研究科, 准教授 (00531691)
安井 学 国立医薬品食品衛生研究所, 変異遺伝部, 室長 (50435707)
Brown John 京都大学, 医学研究科, 講師 (90583188)
津田 雅貴 京都大学, 医学研究科, 特定助教 (00734104)
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| Project Period (FY) |
2016-05-31 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥183,170,000 (Direct Cost: ¥140,900,000、Indirect Cost: ¥42,270,000)
Fiscal Year 2020: ¥35,100,000 (Direct Cost: ¥27,000,000、Indirect Cost: ¥8,100,000)
Fiscal Year 2019: ¥38,090,000 (Direct Cost: ¥29,300,000、Indirect Cost: ¥8,790,000)
Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2016: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
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| Keywords | トキシコロジー / 人体有害物質 / 遺伝毒物学 / 発がん物質 / 変異原 / TK6細胞 / ケモインフォマティクス / QSAR / 抗がん治療薬 |
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| Outline of Final Research Achievements |
We have achieved the following results. First, we created DNA repair enzyme-deficient TK6 strains and have successfully increased by over several times the sensitivity of the thymidine kinase (TK) mutation test stipulated in the Chemical Substances Control Law more than fivefold. We have been creating TK6 mutant strains for rapidly classifying mutagenic chemicals according to their mutagenic mechanisms. We have shown the list of TK6 mutant strains on the TK6 Consortium website and deposited the Riken Biobank. In terms of elucidating new mechanisms for genotoxicity and mutagenicity, we have obtained the following results. We discovered a pathway to repair sex hormone-induced DNA damage and demonstrated that sex hormones are highly genotoxic to epithelial cells in the mammary gland and prostate in the absence of this newly identified pathway. We also discovered a novel DNA damage repair pathway that suppresses formalin-induced mutagenicity.
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義は、性ホルモン及び環境ホルモンの発癌性に関する学術的意義と、新規DNA損傷修復経路を発見である（Saha LK. et al., 2020）。社会的意義は、in silico毒性予測への貢献と、変異原性の作用機序を正確に解明するシステムを構築したことにある。
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| Assessment Rating |
Verification Result (Rating)
A
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Assessment Rating |
Result (Rating)
A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.
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