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O6-Methylguanine-DNA Methyltransferase and uracil DNA glycosylase in human broncho-alveolar lavage cells and peripheral blood mononuclear cells from tobacco smokers and non-smokers
Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute NIH, Bethesda, MD 20892
3Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute NIH, Bethesda, MD 20892
5Pulmonary Disease and Critical Care Division, Georgetown University Medical Center Washington, DC 20007, USA
Because interindividual variations in the activities of DNA repair enzymes may be a risk factor in the pathogenesis of lung diseases, O6-methlguanine-DNA methyltransferase (O6-MT) and uracil DNA glycosylase (UDG) were measured in broncho-alveolar lavage cell (BALC) and peripheral blood mononuclear cell (PBM) samples from 57 healthy volunteers (25 smokers and 32 non-smokers). According to cotinine determination in 39 cases where serum for this was available, 38% of the self-acclaimed non-smokers had >10 ng/ml of cotinine in their serum. Whether grouped into smokers and non-smokers according to clinical history or by serum cotinine, there were no statistically significant differences between these groups in O6-MT or UDG in either of the cell types. However, a tendency towards lower values in smokers was seen. The highest intraindividual variation in O6-MT activity was 7-fold, while the highest interindividual variation reached 18-fold. For UDG, the respective values were 24- and 307-fold. Although the distribution of O6-MT in BALC was different from that in PBM, the data are consistent with unimodality in both of the cell types. These findings suggest that exposure to cigarette smoke is not entirely responsible for the wide interindividual variation in O6-MT and UDG DNA repair activities.
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