职业暴露及其与过敏性喘和肺功能下降的机制联系;数据驱动的方法与挖掘不良结果路径标志相结合
Rob Stierum1, Manosij Ghosh2, Marjolein Meijerink1
1TNO, Risk Analysis for Prevention, Innovation and Development, Zeist, Netherlands.
Frontiers in toxicology
|September 24, 2025
概括
这项研究采用数据驱动的方法,将化学物质暴露与肺功能下降 (LFD) 和过敏喘 (AA) 等呼吸系统疾病联系起来. 它确定了共享的生物途径,为职业健康提供了机制性的见解.
科学领域:
- 职业流行病学 职业流行病学
- 毒素基因组学 毒素基因组学
- 机械毒理学 机械毒理学
背景情况:
- 在职业环境中,建立特定化学物质暴露与健康结果之间的联系是具有挑战性的.
- 传统的流行病学和动物研究在描述复杂暴露和人类相关性方面存在局限性.
- 暴露组概念强调了需要了解各种环境化学物质对健康的影响.
研究的目的:
- 探索一种数据驱动的方法,将化学物质暴露与肺功能下降 (LFD) 和过敏喘 (AA) 联系起来.
- 利用与人类相关的机理学数据,以告知职业化学物质暴露和呼吸道疾病之间的关联.
- 使用毒基因组学和不良结果路径 (AOP) 信息,识别化学物质暴露和LFD/AA之间的共享生物途径.
主要方法:
- 利用公共毒基因组学数据集,在暴露于in vitro柴油超细颗粒 (UFP) 或呼吸道敏感剂的人类呼吸道细胞中识别丰富的基因本体生物学过程 (GO BPs).
- 从分子发起事件 (MIEs) 和关键事件 (KEs) 在不良结果途径 (AOP) 维基和DisGeNET中对LFD和AA进行精选的GOBP.
- 在GO BPs中分析了化学物质暴露和目标呼吸道结果之间的共同点.
主要成果:
- 确定了UFP暴露和LFD之间的GOBP的显著重叠,包括细胞激活和离子传输的调节.
- 在敏感剂暴露和AA之间发现了20个重叠的GOBP,例如对异生菌和氧化应激的反应.
- 鉴定的GOBP提供了可信的机理性见解,尽管AA的体外到体外剂量测量考虑.
结论:
- 使用毒基因组学和AOP数据的数据驱动方法可以提供职业化学物质暴露和呼吸道疾病之间的关联信息.
- 该研究确定了LFD和AA的潜在机制联系,有助于识别职业暴露组中的危险化学物质.
- 有注释的MIE和KE为职业呼吸道疾病研究未来的AOP开发提供了宝贵的资源.
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