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在人类HepaRG细胞中进行错误纠正的下一代测序致变性测定,作为人类相关的遗传毒理新方法方法学方法

A Rasim Barutcu¹, Nimisha Bhattarai¹, Raymond Samuel¹

¹ScitoVation, Durham, NC, United States.

Frontiers in toxicology

|October 1, 2025

概括

在HepaRG细胞中使用双重测序的错误纠正下一代测序 (ecNGS) 准确检测化学变异原体. 这种与人类相关的方法增强了基因毒性测试,支持监管决策.

科学领域:

毒理学毒理学毒理学
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

肝炎RG细胞为遗传毒理学提供了一种与人类相关的新方法方法 (NAM).
修正错误的下一代测序 (ecNGS) 提高了突变性评估的灵敏度和机制洞察力.

研究的目的:

用双重测序来量化HepaRG细胞中化学诱导的点突变,一种ecNGS方法.
评估ecNGS在鉴定基因毒剂突变特征和机制方面的有用性.

主要方法:

双重测序的应用在暴露于乙基甲硫酸盐 (EMS),N-乙基-N-酸盐 (ENU),子[a]烯 (BAP),西斯普拉丁,环胺和埃托胺的HepaRG细胞中.
对突变频率,替代模式和突变特征的分析.
与补充细胞遗传终点的比较.

主要成果:

双重测序检测到ENU和EMS的剂量响应突变,具有特征性的替代模式.
BAP和西斯普拉丁显示突变频率和特定光谱丰富度的适度增加.
埃托胺诱导了细胞遗传反应,但没有点突变,与克拉斯托基性相一致;环胺显示最小的突变性.
科斯米克突变特征分析支持了HepaRG细胞模型的机理相关性.

结论:

ecNGS,特别是双重测序,在检测低频突变和表征机制方面表现出可重现性和特异性.
将ecNGS与细胞遗传试验相结合,可提供全面的,与人类相关的基因毒性评估.
这项研究倡导将ecNGS整合到下一代遗传毒性测试策略中,作为监管用途的NAM.

关键词:

这就是HepaRGG.这个名字是NAM NAM.双层-seqq 是一个双层-seq.ecNGSS 这是一个很好的方法.变异性的城市

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