Carcinogenesis Advance Access published online on August 19, 2004
Carcinogenesis, doi:10.1093/carcin/bgh259
© 2004 by Oxford University Press
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1 Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO, Scientific Institute of Tuscany, Florence, Italy
* To whom correspondence should be addressed. E-mail: stefano.bonassi{at}istge.it.
The recent introduction of biomarkers in population studies of lung cancer has improved the traditional epidemiological approach, especially in the detection of high-risk groups. Many inhalable carcinogens form DNA adducts - an initial event in lung carcinogenesis - and therefore the identification of easily accessible sources of DNA for population studies is considered a leading priority in the field. In this study we compared the frequency of DNA adducts in samples from nasal brushing, bronchial biopsy, and peripheral blood lymphocytes (PBL) in a group of fifty-five subjects - both smokers and non-smokers - undergoing bronchoscopy for diagnostic purposes. Polymorphisms in CYP1A1, GSTM1 and GSTT1 genes were also evaluated. The level of DNA adducts measured by 32P labelling assay in nasal mucosa (108 relative adduct level, mean ± SD; 1.10 ± 0.66) was higher than in bronchial mucosa (0.82 ± 0.36) and in PBL (0.54 ± 0.39; p < 0.01). DNA adducts measured in nasal mucosa and in PBL were correlated with those in bronchial mucosa (p<0.01 and p<0.05 respectively). DNA adducts in smokers were significantly increased in both nasal mucosa and PBL, with a significant dose-response linear trend (p<0.05). No significant effect on DNA adduction of the genetic polymorphisms investigated was found. Nasal mucosa brushing proved to be a suitable procedure for the 32P labelling assay, and its use in population studies should be further explored.
Revised July 20, 2004
Accepted August 2, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms
2 Unit of Environmental Epidemiology and Biostatistics, National Cancer Research Institute, Genoa, Italy
3 Unit of Head and Neck Surgery, National Cancer Research Institute, Genoa, Italy
4 Unit of Pneumology, National Cancer Research Institute, Genoa, Italy; Unit of Pneumology, University of Genoa, Italy
5 Dipartimento di Medicina del Lavoro, Clinica del Lavoro ‘l. Devoto’, University of Milan, Milan, Italy
6 U.O. Pneumologia, Azienda Ospedaliera San Martino, Genoa, Italy
7 Clinica Malattie Apparato Respiratorio & Allergologia DIMI, Azienda Ospedaliera San Martino Università degli Studi, Genoa, Italy
8 Molecular and Genetic Epidemiology Unit, IRCCS, University of Milan, Milan, Italy
9 Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA
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