Investigation the mechanism of 1,2-dichloropropane toxicity using CRISPR screening.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10589
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: National Defense Medical College
• Principal Investigator: Yoshioka Noriyuki 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 衛生学公衆衛生学, 助教 (70365229)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 1,2-ジクロロプロパン / ノックアウトスクリーニング

Outline of Final Research Achievements

As a first step to investigate the toxicity mechanism of 1,2-dichloropropane (DCP), which might be associated with cholangiocarcinogenesis, CRISPR knockout screening was performed to identify which genes are associated with DNA damage in cholangiocyte cell line. A total of 314 genes associated with DNA damage were identified in the knockout screening. Enrichment analysis of the genes suggested that DNA damage caused by DCP exposure is due to reactive oxygen species. We were able to capture the cellular stress response with a knockout screening.

Free Research Field

衛生学

Academic Significance and Societal Importance of the Research Achievements

本研究ではCRISPRノックアウトスクリーニングにより胆管がん発生と関連するとされる1,2-dichloropropane (DCP)について、その代謝産物による胆管細胞のDNA損傷が活性酸素によることが示唆された。この結果は近年の科学技術の発展に伴う新しい技術が毒性学にも応用可能であることを示唆している。