Establishment of high-throughput screening of toxic chemical compounds.

2015 Fiscal Year Final Research Report

• Project/Area Number: 23221005
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: Takeda Shunichi 京都大学, 医学(系)研究科(研究院), 教授 (60188191)
• Co-Investigator(Kenkyū-buntansha): HIROTA Kouji 首都大学東京, 大学院理工学研究科, 教授 (00342840) ; YAMADA Ryo 京都大学, 大学院医学研究科, 教授 (50301106) ; OKADA Tetsuya 京都大学, 大学院理学研究科, 助教 (70378529) ; SASANUMA Hiroyuki 京都大学, 大学院医学研究科, 准教授 (00531691)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Hiroyasu 大阪医科大学, 医学部, 准教授 (60340551) ; TAKAHASHI Ryosuke 京都大学, 大学院医学研究科, 教授 (90216771)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 有害化学物質 / 化審法 / 遺伝毒物学 / 発がん物質 / 変異原 / 小核実験 / ハイスループットスクリーニング / レギュラトリーサイエンス

Outline of Final Research Achievements

Isogenic chicken DT40 B-lymphocyte cell lines deficient in DNA repair pathways can be used to identify genotoxic compounds. As part of the US Tox21 program, we optimised several different DT40 isogenic clones on a high-throughput screening platform and confirmed the utility of this approach for detecting genotoxicants by measuring differential cytotoxicity in wild-type and DNA repair-deficient clones following chemical exposure. We then screened the Tox21 10K golden-standard chemical compound library, and demonstrate the utility of this chemical-genetic approach for identifying and prioritising compounds that may damage DNA.
To improve the bioassay of detecting genotoxicants, we established a method of disrupting genes in the human TK6 B cell line, a standard cell line for identifying genotoxicants by OECD countries. We have already generated ~20 TK6 mutants dedficient in various DNA-repair-genes.

Free Research Field

分子生物学