Association between O6-alkylguanine-DNA-alkyltransferase activity in peripheral blood lymphocytes and bronchial epithelial cells.
The activity of the DNA repair enzyme O6-alkylguanine-DNA-alkyltransferase (ATase) may be a risk factor in the pathogenesis of lung cancer. ATase activity 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 these samples correlates well with the activity found in bronchial epithelial cells, the progenitor cells for the main types of lung cancer. In this study, 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 correlation in ATase levels was observed between any of the three samples. We conclude that bronchial brushing is a more specific and reliable way of sampling bronchial epithelial cells than BL and that it samples enough cells for ATase activity to be determined. In addition, in terms of the activity of this potentially critical DNA repair enzyme, PBLs, and cell extracts obtained from BL may not provide good surrogate tissue for bronchial epithelial cells, the critical targets for carcinogenesis.
O'Donnell
P N
PN
CRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.
Barber
P V
PV
Margison
G P
GP
Povey
A C
AC
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D001706:Biopsy; D001980:Bronchi / Q000201:enzymology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D004260:DNA Repair; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009713:Nucleotidyltransferases / Q000378:metabolism*; D012016:Reference Values; D012907:Smoking / Q000009:adverse effects
D009713:Nucleotidyltransferases; C020658:glutamine-synthetase adenylyltransferase