Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells.
AuthorsPovey, Andrew C
Barber, Philip V
Watson, Amanda J
Margison, Geoffrey P
Santibanez-Koref, Mauro F
AffiliationCentre for Occupational and Environmental Health, University of Manchester, Manchester, United Kingdom. firstname.lastname@example.org
MetadataShow full item record
AbstractO6-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.
CitationSmoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells. 2006, 119 (2):463-6 Int. J. Cancer
JournalInternational Journal of Cancer.
- Association between O6-alkylguanine-DNA-alkyltransferase activity in peripheral blood lymphocytes and bronchial epithelial cells.
- Authors: O'Donnell PN, Barber PV, Margison GP, Povey AC
- Issue date: 1999 Jul
- Topographical study of O(6)-alkylguanine DNA alkyltransferase repair activity and N7-methylguanine levels in resected lung tissue.
- Authors: Crosbie PA, Harrison K, Shah R, Watson AJ, Agius R, Barber PV, Margison GP, Povey AC
- Issue date: 2013 Jul 5
- O(6)-methylguanine-DNA methyltransferase (MGMT): impact on cancer risk in response to tobacco smoke.
- Authors: Christmann M, Kaina B
- Issue date: 2012 Aug 1
- Reduced lung tumorigenesis in human methylguanine DNA--methyltransferase transgenic mice achieved by expression of transgene within the target cell.
- Authors: Liu L, Qin X, Gerson SL
- Issue date: 1999 Feb
- Mice over-expressing human O6 alkylguanine-DNA alkyltransferase selectively reduce O6 methylguanine mediated carcinogenic mutations to threshold levels after N-methyl-N-nitrosourea.
- Authors: Allay E, Veigl M, Gerson SL
- Issue date: 1999 Jun 24