オーラルセッション
- 第1日 6月22日（水） 17:30～17:45 D会場（413，414）
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1D-O1-1730（1P-46） PDF
ヒト初代肝細胞のマルチオミクス解析を基盤とした薬物誘発性肝障害評価法の開発
Drug-induced liver injury (DILI) is a significant cause of failure for valuable drug candidates in clinical trials and post-marketing. However, conventional hepatotoxicity assessments to avoid DILI at an early stage cannot assess the combined toxicity or elucidate the mechanism leading to each toxicity. In this study, we proposed a new hepatotoxicity evaluation method based on multi-omics analysis (drug metabolism analysis, metabolomics, and proteomics) using an optimized sample pretreatment and introduction method from 1 × 104 primary human hepatocytes (PHH) cultured on a 96-well plate. To achieve multi-omics analysis with a small number of PHH, we optimized the sample preparation process using 96-well plates and investigated the method of introducing the small amount of sample to LC/MS. We then obtained multi-omics information from PHHs exposed to acetaminophen, determined by cell viability (inhibitory concentration, IC). The previously reported acetaminophen metabolites have been identified, and we have succeeded in detecting endogenous metabolites and proteins that fluctuate below IC10. The multi-omics analytical system using PHH is expected to be used as a novel DILI evaluation method that can discover drug toxicity expression pathways and safety biomarkers.