Molecular epidemiology studies on occupational and environmental exposure to mutagens and carcinogens, 1997-1999

Molecular epidemiology is a new and evolving area of research, combining la boratory measurement of internal dose, biologically effective dose, biologi c effects, and influence of individual susceptibility with epidemiologic me thodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure-metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect-chromosomal aberrations, s ister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guani ne phosphoribosyltransferase gene, and the activation of oncogenes coding f or p53 or p21 proteins as measured on protein levels; biomarkers of suscept ibility-genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA addu cts measured by P-32-postlabeling are the biomarker of choice for the evalu ation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarker s of effect, the most common are cytogenetic end points. Epidemiologic stud ies support the use of chromosomal breakage as a relevant biomarker of canc er risk. The use of the Comet assay and methods analyzing oxidative DNA dam age needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens.