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利用CometChip测定方法检测PAH诱导的DNA大容量添加物在3D初级人类支气管上皮细胞模型中

Victoria C Colvin¹, Norah A Owiti², Bevin P Engelward²

¹Department of Environmental and Molecular Toxicology, USA; OSU/PNNL Superfund Research Program, Oregon State University, Corvallis, OR, USA.

|July 25, 2025

概括

初级人类支气管上皮细胞 (HBECs) 可以检测出像 (BAP) 这样的多环芳 (PAHs) 造成的DNA损伤. 这项研究表明,HBECs是PAH毒性评估的敏感工具.

科学领域:

毒理学毒理学毒理学
细胞生物学细胞生物学
环境健康环境健康

背景情况:

多环芳 (PAH) 是燃烧的副产品,通过DNA损伤与癌症有关.
人类支气管上皮细胞 (HBEC) 是吸入PAH暴露的相关模型.
评估HBECs中PAH诱导的DNA损伤需要了解它们的代谢激活能力.

研究的目的:

评估人类支气管上皮细胞 (HBECs) 通过暴露于[a]烯 (BAP) 来调节DNA损伤的能力.
为了比较单层和空气-液体接口 (ALI) HBEC培养中的DNA损伤反应.
评估CometChip测定用于检测HBECs中BAP诱导的DNA损伤的灵敏度.

主要方法:

利用CometChip测定来测量暴露于BAP的单层和ALI培养HBECs中的DNA损伤.
采用HepG2细胞作为阳性代谢对照和MEF细胞作为负控.
监测CYP1A1活性,细胞毒性和屏障完整性作为次要终点.

主要成果:

单层和ALI-HBEC都显示了BAP诱导的DNA损伤的剂量依赖性增加,类似于HepG2细胞.
单层HBECs对DNA损伤的敏感性高于ALI-HBECs,与CYP1A1活性相关.
彗星芯片测定检测到DNA损伤的BAP度低于其他测量的终点.

结论:

特别是单层培养中的HBECs能够对BAP进行代谢激活,从而导致DNA损伤.
彗星芯片测定是一种敏感的方法,用于评估HBECs中BAP诱导的DNA损伤.
这些发现支持在吸入PAH的定量毒性评估中使用HBECs.

关键词:

[a]二烯是一种基二烯.支气管上皮细胞是支气管上皮细胞.彗星测量试验方法细胞染色体P450 1A1 1A1 1A1 1A1 1A1 1A1 细胞染色体P450 1A1 1A1 细胞染色体造成的DNA损伤是DNA损伤.多环芳香碳化合物多环芳香碳化合物

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