14 The Development and Characterisation of Novel Monoclonal Antibodies (Mabs) for 1-Hydroxypyrene Glucuronide (1-OHPyrG) Determination and Polycyclic Aromatic Hydrocarbon (PAH) Biomonitoring

Autor: Lathan Ball, Claire Baker, Harry Carter, Kate Jones
Rok vydání: 2023
Předmět:
Zdroj: Annals of Work Exposures and Health. 67:i18-i19
ISSN: 2398-7316
2398-7308
DOI: 10.1093/annweh/wxac087.048
Popis: Objective PAHs are produced during the incomplete burning of organic materials. PAH sources include vehicle exhaust, tobacco smoke and waste incineration. Cancer is a significant endpoint of PAH exposure. Pyrene is a common component of PAH exposures and metabolism of pyrene leads to the excretion of 1-OHPyrG in urine. Measurement of 1-OHPyrG has been used to assess occupational and environmental exposure to PAHs. The production of Mabs to 1-OHPyrG will allow the development of novel PAH biomonitoring tests, facilitating the introduction of routine screening and safeguarding human health. Methods 1-Pyrenebutyric acid was coupled to a carrier protein and a sheep Mab raised to 1-OHPyrG. A second Mab which binds the Mab-1-OHPyrG immune complex was also produced and a novel urinary non-competitive ELISA developed. Careful formulation of assay buffers has overcome the heterogeneous nature of urine. Assay performance was confirmed through binding studies with structurally similar metabolites, reproducibility testing and a comparative method study. Results A sensitive and specific ELISA (measuring range 20-500pg/ml) was used to detect elevated levels of 1-OHPyrG in urine. Occupational samples determined by ELISA and HPLC-fluorescence were in good agreement (R2=0.91, N=20). A test kit is now being transferred to manufacture. Conclusions The development of a novel ELISA for 1-OHPyrG has allowed the production of a sensitive and specific PAH biomonitoring test kit. Kits increase the accessibility of biomonitoring and facilitate the introduction of routine screening. Alternate assay formats are being investigated. A lateral flow “point of care” test will enable on-site testing and significantly increase the utility of biomonitoring.
Databáze: OpenAIRE
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