Use of biomarkers--new frontiers in occupational toxicology and epidemiology

The incorporation of biomarkers into occupational toxicology and epidemiology some 25 years ago marked a turning-point for the discipline. The advances in molecular biology have provided new tools. At first, the major interest was in biomarkers of exposure, borrowing concepts from pharmacology, then it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. Concerted efforts to measure carcinogens at the molecular level, e.g. DNA adducts, occupied a substantial fraction of the biomarkers work. In parallel, more quantitative and more sensitive end-points for etiological studies were sought earlier. Again, with advancing techniques in cytogenetics, extensive studies were conducted on such markers as sister chromatid exchanges (SCEs), micronuclei and other changes deemed to represent genomic damage. However, these types of end-points were quite unspecific for application to new hazards of uncertain human carcinogenic potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced mechanistic insight. The advances in molecular genetics have led to an upsurge in interest in most susceptibility factors, and identification of polymorphisms of various enzymes has become possible. Ongoing search for 'ultra-high risk' individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a small differential risk, however theoretically or mechanistically important, offer only little practical use.