The development of rapid immunoassays for the urinary analysis of 1-hydroxypyrene glucuronide facilitate both laboratory and on-site polycyclic aromatic hydrocarbon biomonitoring

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2024-10-03 DOI:10.1016/j.toxlet.2024.10.002

Lathan Ball , H. Carter , C. Baker , R. Porter

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Abstract

Polycylic Aromatic Hydrocarbons (PAHs) are produced during the incomplete burning of organic materials. PAH sources include vehicle exhaust, tobacco smoke and waste incineration. Environmental and occupational exposures to PAHs are known to occur. Cancer is a significant endpoint of PAH exposure and several occupations associated with high PAH exposure have been classified by IARC as carcinogenic to humans (Group 1).

Pyrene is a common component of PAH mixtures and metabolism of pyrene leads to the excretion of 1-hydroxypyrene glucuronide (1-OHPyrG) in urine. Laboratory measurement of urinary 1-OHPyrG is employed in occupational and environmental biomonitoring programmes. The production of an anti-1-OHPyrG monoclonal antibody would allow the development of a PAH biomonitoring ELISA facilitating large scale laboratory screening and routine testing.

The development of a lateral flow immunoassay and the production of a field test (point of use test) would greatly increase the value of biomonitoring. A novel Lateral Flow has been developed which employs an anti-1-OHPyrG sheep monoclonal antibody (Mab) to capture the PAH metabolite. The captured metabolite is visualised through a second Mab raised against the Mab-1-OHPyrG immune complex. This sandwich assay provides a positive correlation between the assay signal and biomarker concentration.

A Smartphone camera allows signal measurement and a carefully considered ‘app’ provides result interpretation and data analysis. Results are provided in an exposed/not-exposed format. Performance of the lateral flow was confirmed through a comparative study and field trial. The development of a lateral flow test provides "real-time" analysis to occupational health professionals. On-site screening allows the immediate confirmation of safe working practice, provides immediate reassurance to those involved in potentially hazardous activities and greatly increases the efficacy of biomonitoring.

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开发用于尿液中 1-羟基芘葡萄糖醛酸分析的快速免疫测定，有助于实验室和现场多环芳烃生物监测。

多环芳烃（PAHs）是在有机物不完全燃烧的过程中产生的。PAH 的来源包括汽车尾气、烟草烟雾和垃圾焚烧。众所周知，环境和职业中都会接触到 PAHs。癌症是接触 PAH 的一个重要终点，国际癌症研究机构已将与大量接触 PAH 相关的几种职业列为对人类致癌的职业（第 1 类）。芘是 PAH 混合物中的常见成分，芘的新陈代谢会导致尿液中排出 1- 羟基芘葡萄糖醛酸苷（1-OHPyrG）。职业和环境生物监测计划中采用了尿液 1-OHPyrG 实验室测量法。抗 1-OHPyrG 单克隆抗体的生产将有助于多环芳烃生物监测 ELISA 的开发，从而促进大规模的实验室筛选和常规检测。开发侧流免疫测定法和生产现场测试（使用点测试）将大大提高生物监测的价值。目前已开发出一种新型侧向流免疫测定法，利用抗-1-OHPyrG 羊单克隆抗体（Mab）来捕获 PAH 代谢物。捕获的代谢物通过针对 Mab-1-OHPyrG 免疫复合物的第二种单克隆抗体显现出来。这种夹心检测法可在检测信号和生物标记物浓度之间建立正相关。智能手机摄像头可以测量信号，精心设计的 "应用程序 "可以提供结果解释和数据分析。结果以暴露/非暴露格式提供。横向流动的性能已通过比较研究和现场试验得到确认。侧向流测试的开发为职业健康专业人员提供了 "实时 "分析。现场筛查可以立即确认安全的工作方法，为参与潜在危险活动的人员提供即时的保证，并大大提高生物监测的效率。

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