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Refinement of a Methodology for Untargeted Detection of Serum Albumin Adducts in Human Populations

Research output: Contribution to journalArticle

George W. Preston, Michelle Plusquin, Osman Sozeri, Karin Van Veldhoven, Lilian Bastian, Tim S. Nawrot, Marc Chadeau-Hyam, David H. Phillips

Original languageEnglish
Pages (from-to)2120-2129
JournalChemical Research in Toxicology
Volume30
Issue number12
Early online date17 Nov 2017
DOIs
Publication statusPublished - 18 Dec 2017

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Abstract

Covalently modified blood proteins (e.g., serum albumin adducts) are increasingly being viewed as potential biomarkers via which the environmental causes of human diseases may be understood. The notion that some (perhaps many) modifications have yet to be discovered has led to the development of untargeted adductomics methods, which attempt to capture entire populations of adducts. One such method is fixed-step selected reaction monitoring (FS-SRM), which analyses distributions of serum albumin adducts via shifts in the mass of a tryptic peptide [Li et al. (2011) Mol. Cell. Proteomics 10, M110.004606]. Working on the basis that FS-SRM might be able to detect biological variation due to environmental factors, we aimed to scale the methodology for use in an epidemiological setting. Development of sample preparation methods led to a batch workflow with increased throughput and provision for quality control. Challenges posed by technical and biological variation were addressed in the processing and interpretation of the data. A pilot study of 20 smokers and 20 never-smokers provided evidence of an effect of smoking on levels of putative serum albumin adducts. Differences between smokers and never-smokers were most apparent in putative adducts with net gains in mass between 105 and 114 Da (relative to unmodified albumin). The findings suggest that our implementation of FS-SRM could be useful for studying other environmental factors with relevance to human health.

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