Macromolecule adducts as biomarkers of exposure to environmental mutagens in human populations

A cancer epidemiologist recently said that "adduct measurement has so far been of little use to epidemiological research." This remark gives us a starting point for the discussion of the purposes of measuring macromolecule adducts that originate from electrophilic compounds or metabolites in humans and animals. Historically, methods for adduct monitoring were developed as a means of determining target doses that, combined with measurements of genotoxic potencies, could be used for risk assessment. With mass spectrometric methods, adducts can be quantified at levels that are thousands of times lower than those in which the cancer incidence associated with this exposure is detectable in disease-epidemiological studies. Furthermore, mass spectrometric techniques permit identification of the chemical structure of the adduct, particularly in the case of hemoglobin adducts. Adduct measurement therefore constitutes not only a means of risk estimation but it may be used as a complement of disease epidemiology in situations in which, for statistical reasons, the risk is too low to be detectable--which does not signify that the risk is acceptably low. It also gives a possibility of identification of the dangerous components in mixed exposures and of the relevant reactive intermediates in cases of complex metabolism.