[Biologically effective dose biomarkers]

Biologically effective dose markers--DNA and protein adducts--are classified among exposure biomarkers, and are currently used to assess the biologically active fraction of xenobiotics, which is capable of interacting with cellular macromolecules at the target site. Macromolecular adducts should not only be considered as exposure indicators; indeed, their biological significance can also be extended to biomarkers of effect and of susceptibility. The achievement of such a goal needs research programs aimed both at studying molecular mechanisms related to each step along the continuum of events between exposure and disease, and at establishing quantitative relationships between exposure levels and adduct formation, between adducts and early biological effects, effects and cellular structural/functional modifications, leading to the development and eventual increase in incidence of specific diseases. Moreover, different factors must be considered during data evaluation, such as interindividual variability, the background levels of biomarkers in non occupationally exposed population, the gradually decreasing doses of genotoxic agents involved in occupational exposure, and confounding factors such as diet and smoking habits. Despite the large body of literature documenting DNA and protein adduct molecular dosimetry for many carcinogen exposures, many authors highlight the need for systematic interlaboratory comparison and collaboration by measuring the same biomarkers using different techniques and/or different biomarkers related to the same exposure levels. There is also general agreement about reducing costs, so that dosimetric analyses can become economically more advantageous and accessible in all cases where they prove to be useful in preventing health risks.