BIOMONITORING HUMAN EXPOSURE TO ENVIRONMENTAL CARCINOGENIC CHEMICALS

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to en vironmental genotoxic pollutants, The procedures used involved both di rect measurement of DNA or protein damage (adducts) and assessment of secondary biological effects (mutation and cytogenetic damage), Adduct detection at the level of DNA or protein (haemoglobin) was carried ou t by P-32-postlabelling, immunochemical, HPLC or mass spectrometric me thods, Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry), The measurement o f adducts was focused on those from genotoxicants that result from pet rochemical combustion or processing, e,g, low-molecular-weight alkylat ing agents, PAHs and compounds that cause oxidative DNA damage. Cytoge netic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes invol ved in cancer development, Blood and urine samples from individuals ex posed to urban pollution were collected, Populations exposed through o ccupational or medical sources to larger amounts of some of the genoto xic compounds present in the environmental samples were used as positi ve controls for the environmentally exposed population, Samples from r ural areas were used as negative controls, The project has led to new, more sensitive and more selective approaches for detecting carcinogen -induced damage to DNA and proteins, and subsequent biological effects , These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in work ers in a coke oven plant, garage workers exposed to diesel exhaust aci d workers exposed to ethylene oxide in a sterilization plant, Dose res ponse and adduct repair were studied for methylated adducts in patient s treated with methylating cytostatic drugs, The biomonitoring methods have also demonstrated their potential for detecting environmental ex posure to genotoxic compounds in nine groups of non-smoking individual s, P-32-postlabelling of DNA adducts being shown to have the greatest sensitivity.