Association between O-6-alkylguanine-DNA- alkyltransferase activity in peripheral blood lymphocytes and bronchial epithelial cells

The activity of the DNA repair enzyme O-6-alkylguanine-DNA-alkyltransferase (ATase) may be a risk factor in the pathogenesis of lung cancer. ATase act ivity has previously been measured in peripheral blood lymphocytes (PBLs), cell extracts from bronchoalveolar lavage fluid, and cell homogenates from resected lung tissue. However, it is not clear whether ATase activity in th ese samples correlates well with the activity found in bronchial epithelial cells, the progenitor cells for the main types of lung cancer. In this stu dy, cell extracts were prepared from PBLs, bronchial lavage (BL) fluid, and bronchial brushings from normal lung in 20 patients attending for routine bronchoscopy. Bronchial brushing sampled a significantly greater proportion of bronchial epithelial cells than did BL [88 +/- 9% (mean +/- SD) versus 39 +/- 19%; P < 0.0001]. ATase activity was determined in each of the cell extracts and was found to be higher in PBLs than in bronchial brushings (P = 0.005 ) and higher in bronchial brushings than in BL (P = 0.005), No corr elation in ATase levels was observed between any of the three samples. We c onclude that bronchial brushing is a more specific and reliable way of samp ling bronchial epithelial cells than BL and that it samples enough cells fo r ATase activity to be determined. In addition, in terms of the activity of this potentially critical DNA repair enzyme, PBLs, and cell extracts obtai ned from BL may not provide good surrogate tissue for bronchial epithelial cells, the critical targets for carcinogenesis.