Study on rapid and hypersensitive screening of chemical genotoxin using mammalian cells defective for DNA damage-response factors

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K14953
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Gakushuin University
• Principal Investigator: HANAOKA Fumio 学習院大学, 理学部, 研究員 (50012670)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ゲノム / DNA損傷 / 損傷乗り越え合成 / 損傷応答 / 遺伝毒性 / スクリーニング系 / マウス胚性線維芽細胞

Outline of Final Research Achievements

In order to establish a rapid, simple and hypersensitive method of screening various genotoxic compounds for mammalian cells, we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type (WT) and knock-out mice lacking one of three Y-family TLS DNA polymerases (Pol eta, Pol iota, and Pol kappa) or all of them (TKO). We found that TKO cells exhibited the highest sensitivities to most of the tested genotoxins, but not to the non-genotoxins. Furthermore, we found that ratios of half-maximal inhibitory concentration of WT and TKO cells would be nice markers to quantitatively evaluate the hypersensitivity of TKO cells to different chemicals.

Free Research Field

分子生物学