Superfund Research Program
Biomarkers of Asbestos Exposure
Exposure biomarkers can be used to assess the amount of a chemical that is present within the body. However, asbestos is not present in readily accessible biological fluids; it is inhaled and trapped in lung tissue for long periods of time and so reproducible analytical techniques are critical to ensuring proper validation. Once fully validated and characterized, biomarkers can serve a critical role in detecting levels of exposure, allowing gene-environment interactions to be assessed. The high mobility group box 1 (HMGB1) and its acetylated proteoforms are reported to be a promising biomarker for malignant mesothelioma and asbestos exposure. To overcome the numerous problems with immunoassay-based methodology, the Biomarkers of Asbestos Exposure Project, conducted by Ian A. Blair, Ph.D., Anil Vachani, Ph.D., and their researchers have developed a specific and sensitive assay based on stable isotope dilution and immunopurification to quantify HMGB1 in plasma and serum. The method employed two-dimensional (2D)-nano-ultra high-performance liquid chromatography-parallel reaction monitoring/high resolution mass spectrometry (Weng L, Guo L, Vachani A, Mesaros C, Blair IA. Anal. Chem., 2018). Using this assay, plasma HMGB1 levels were much lower than serum levels, which conclusively demonstrated that HMGB1 was secreted when blood is allowed to clot. Moreover, no endogenous acetylation was detected on HMGB1 in healthy control serum. This exciting new method will evaluate HMGB1 and fibuin-3 proteoforms as biomarkers of asbestos exposure and asbestos-related diseases under the auspices of the Remediation of Asbestos Particles Project in the renewal application.