DNA ADDUCTS AS A MEASURE OF LUNG-CANCER RISK IN HUMANS EXPOSED TO POLYCYCLIC AROMATIC-HYDROCARBONS

Workers in the coking, foundry, and aluminum industry can be exposed t o high concentrations of polycyclic aromatic hydrocarbons (PAHs) and a re at increased risk for lung cancer, as are cigarette smokers. In rec ent years several studies on workers in the foundry and coking industr ies have been reported. In these studies, white blood cell (WBC) DNA w as used for analysis of PAH-DNA adducts. Theoretically, DNA adduct for mation is a more relevant biological parameter for assessing exposure risk than PAH in the work atmosphere, or the amount of a metabolite in the urine, because adduct levels reflect that part of the dose that e scapes detoxification and binds to DNA. We analyzed WBC DNA from coke- oven workers and from workers in an aluminum production plant and demo nstrated the presence of PAH-DNA adducts. Forty-seven percent of the c oke-oven workers had detectable levels of PAH-DNA adducts in their WBC compared with 27% of the controls (p < 0.05), measured with ELISA. In both groups, smokers had significantly higher levels of PAH-DNA adduc ts than did nonsmokers. In the aluminum workers, no PAH-DNA adducts we re detected by ELISA, although the benzo[a]pyrene concentrations in th e work atmosphere were comparable to those of the coke-oven workers. T he more sensitive P-32-postlabeling assay showed the presence of PAH-D NA adducts in 91% of the aluminum workers. There was no correlation of WBC adduct levels with the concentration of PAH in the work atmospher e. Recently we showed that total PAH-DNA adduct levels in WBC from lun g cancer patients were much higher than those generally found in healt hy smokers. These increased adduct levels may indicate a subpopulation of smokers with increased risk for lung cancer, resulting from a gene tic predisposition in this group of persons. Because WBCs are not the target cells for exposure-related cancer, the relationship between PAH -DNA adducts in the lung and in WBCs remains to be established.