Protein adductomics: Analytical developments and applications in human biomonitoring

Proteins contain many sites that are subject to modification by electrophiles. Detection and characterisation of these modifications can give insights into environmental agents and endogenous processes that may be contributing factors to chronic human diseases. An untargeted approach, utilising mass spectrometry to detect modified amino acids or peptides, has been applied to blood proteins haemoglobin and albumin, focusing in particular on the N-terminal valine residue of haemoglobin and the cysteine-34 residue in albumin. Technical developments to firstly detect simultaneously multiple adducts at these sites and then subsequently to identify them are reviewed here. Recent studies in which the methods have been applied to biomonitoring human exposure to environmental toxicants are described. With advances in sensitivity, high-throughput handling of samples and robust quality control, these methods have considerable potential for identifying causes of human chronic disease and of identifying individuals at risk.