Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells.

Abstract:

: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.

journal_name

Int J Cancer

authors

Povey AC,O'Donnell P,Barber P,Watson M,Margison GP,Santibáñez Koref MF

doi

10.1002/ijc.21790

keywords:

subject

Has Abstract

pub_date

2006-07-15 00:00:00

pages

463-6

issue

2

eissn

0020-7136

issn

1097-0215

journal_volume

119

pub_type

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