长期暴露于PFAS会触发独立于其生物积累的系统级细胞重编程
bioRxiv : the preprint server for biology
|July 17, 2025
概括
在长期,低剂量暴露后,Per-和多醇基物质 (PFAS) 引发细胞变化. 这些"永远的化学物质"激活氧化应激,改变脂质代谢,随着时间的推移揭示复杂的细胞反应.
科学领域:
- 环境毒理学环境毒理学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 被称为"永恒化学品"的Per-和多基基物质 (PFAS) 是无处不在的环境污染物.
- 暴露于PFAS与各种健康问题有关,包括代谢,免疫和神经毒性疾病.
- 在环境相关度下,PFAS毒性背后的长期细胞机制尚未完全理解.
研究的目的:
- 为了研究低度,环境相关的高酸 (PFOA) 和高酸硫酸 (PFOS) 的慢性细胞效应.
- 为了阐明PFAS毒性的分子机制,在人类上皮细胞中使用时间解决的多原子方法.
主要方法:
- 使用了24周的慢性暴露模型与非转化的人类上皮细胞.
- 应用集成的转录组和脂组分析来评估细胞反应.
- 在暴露期间监测细胞积累和分子变化.
主要成果:
- 观察到PFOA和PFOS的最小细胞积累.
- 在暴露17周左右出现了显著的分子变化.
- 关键发现包括氧化应激反应 (例如,SESN2,SOD3),细胞生存途径和脂质代谢 (SREBP轴) 的激活.
- 确定了膜脂质组成中的化合物特异性破坏.
结论:
- 慢性,低剂量的PFAS暴露会诱导复杂的细胞反应,包括氧化应激和改变的脂质代谢.
- 时间解析的多原子分析对于了解慢性化学暴露的机制至关重要.
- 这些发现为进一步对PFAS毒性进行体内研究提供了基础.
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