COMPARISON OF DNA ADDUCTS FROM EXPOSURE TO COMPLEX-MIXTURES IN VARIOUS HUMAN TISSUES AND EXPERIMENTAL SYSTEMS

DNA adducts derived from complex mixtures of polycyclic aromatic compo unds emitted from tobacco smoke are compared to industrial pollution s ources (e.g., coke ovens and aluminum smelters), smoky coal burning, a nd urban air pollution. Exposures to coke oven emissions and smoky coa l, both potent rodent skin tumor initiators and lung carcinogens in hu mans, result in high levels of DNA adducts compared to tobacco smoke i n the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human s tudies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sper m, and autopsy tissues of smokers and nonsmokers Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavag e cells. Comparison of the DNA adduct levels resulting from human expo sure to different complex mixtures shows that emissions from coke oven s, aluminum smelters, and smoky coal result in higher DNA adduct level s than tobacco smoke exposure. These studies suggest that humans expos ed to complex combustion mixtures will have higher DNA adduct levels i n target cells (e.g., lung) as compared to nontarget cells (e.g., lymp hocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture.