Pivotal Role of Mass Spectrometry for the Assessment of Exposure to Reactive Chemical Contaminants: From the Exposome to the Adductome.

A large part of the Human chemical exposome is now well characterized, and its health effects has been widely documented, although precise causal links remain difficult to establish. In parallel, genetic factors only were shown to contribute less than 30% to various pathologies. Therefore, environmental factors may represent the predominant cause of chronic diseases. Mass Spectrometry has been established for many years as a main "gold standard" in this field due to its performances both in sensitivity and selectivity. However, some unstable or highly reactive compounds may escape their detection in the biological samples because of their short half-life although some of their stable metabolites, if any, can be used for the exposure assessment. These electrophilic molecules are known to bind covalently to nucleophilic molecules in the body to form what are commonly called adducts. The study of adducts formed with DNA, proteins or with glutathione, nowadays called adductomics, can provide additional toxicologically relevant information in biomonitoring studies. This review describes this particular part of the reactive exposome and the related mass spectrometric methods developed therein. Three dedicated parts of this review are devoted to the contribution of mass spectrometry respectively to the assessment of DNA modifications, protein modifications, and reaction with glutathione.