Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells.
O6-alkylguanine-DNA alkyltransferase (MGMT) represents the first line of defense against the toxic, mutagenic and carcinogenic effects of O6-alkylguanine adducts in DNA. These adducts mediate the biological activity from a series of alkylating agents, such as the tobacco-specific nitrosamines, believed to contribute to the carcinogenicity of tobacco smoke. There have been conflicting reports on the effects of smoking on MGMT activity in lung and other tissues. Here, we investigate MGMT activity in peripheral blood mononuclear cells (PBMC) and lung bronchial epithelial cells (BEC), extracted by lung brushings, from smokers and nonsmokers attending a bronchoscopy clinic. MGMT activity was significantly lower in BECs (geometric mean; 95% confidence interval 1.02; 0.86-1.20 fmol/microg DNA) than in PBMCs (7.86; 6.70-9.59 fmol/microg DNA; p < 0.001), suggesting that bronchial epithelia may be particularly sensitive to alkylation damage. More importantly our results indicate that activity in BECs is significantly decreased in samples from current smokers (0.71; 0.54-0.93 fmol/microg DNA) compared to nonsmokers (1.25; 1.03-1.51 fmol/microg DNA; p = 0.002). This could represent an important contribution to the carcinogenicity of tobacco smoke.
Centre for Occupational and Environmental Health, University of Manchester, Manchester, United Kingdom. a.povey@manchester.ac.uk
Andrew C
AC
Povey
Paul
P
O'Donnell
Phil
P
Barber
Mandy
M
Watson
Geoffrey P
GP
Margison
Mauro F
MF
Santibáñez Koref
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000201:enzymology*; D001999:Bronchoscopy; D002273:Carcinogens; D018736:DNA Adducts / Q000009:adverse effects; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*
D002273:Carcinogens; D018736:DNA Adducts; D019853:O(6)-Methylguanine-DNA Methyltransferase