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Polycyclic aromatic hydrocarbon—DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute (Antoni, van Leeuwenhoek Huis) 121 Plesmanlaan, 1066 CX Amsterdam
1Present address: Departisient of Health Risk Analysis, University of Limburg Becldsnijdersdreef 101, 6200 MD Maastricht, The Netherlands
2Division of Psychosocial Research, The Netherlands Cancer Institute (Antoni, van Leeuwenhoek Huis) 121 Plesmanlaan, 1066 CX Amsterdam
3Division of Clinical Oncology, The Netherlands Cancer Institute (Antoni, van Leeuwenhoek Huis) 121 Plesmanlaan, 1066 CX Amsterdam
4Department of Pulmonology, University Hospital of Amsterdam. Academic Medical Center 15 Meibergdreef, 1105 AZ Amsterdam, Thc Netherlands
5To whom correspondence should be addressed
Smokers of cigarettes are exposed to a number of carcinogens, induding polycylic aromatic hydrocarbons (PAHs), and are at a high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation to reactive intermediates that can damage DNA through adduct formation. Measuring DNA adducts in peripheral white blood cells (WBC) could serve as a means of monitoring human exposure to genotoxic agents and subsequently risk assessment. In this study, DNA from WBC obtained from 39 lung cancer patients was examined for PAH-DNA adducts both in an ELISA using a polyclonal antibody against benzo[a]pyrene 7,8-diol-9,10-epoxide (BPDE)-DNA and the 32P-post-labeling technique. The ELISA results showed BPDE-DNA antigenicity in WBC DNA from 12/38 (32%) patients and adduct levels ranged from 1.5 to >150 adducts in 108 nucleotides. The autoradiographs of chromatograms of 32P-post-labeled digests of WBC DNA from the 38 patients showed a variety of adduct spots; relative adduct labeling (RAL) values ranged from 0.3 to 407 adducts in 108 nucleotides. In 18 of the 38 (47%) persons an adduct spot was detected that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG); RAL values ranged from 0.03 to 382 adducts in 108 nucleotides. Correlations were not significant between the adduct levels in WBC and smoking habits, age or sex. From 20 patients of the same group lung tissue was collected at surgery and examined for PAH-DNA adducts by ELISA and 32P-post-labeling assay. No significant correlation was found between DNA adduct levels in blood and lung. This finding stresses the limitations of the use of WBC as a surrogate for adduct levels in the target organ.
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