Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms.
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 55 subjects, both smokers and non-smokers, undergoing bronchoscopy for diagnostic purposes. Polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes were also evaluated. The level of DNA adducts measured by (32)P-labelling assay in nasal mucosa (10(8) 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 (32)P-labelling assay and its use in population studies should be further explored.
Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO, Scientific Institute of Tuscany, Florence, Italy.
Marco
M
Peluso
Monica
M
Neri
Giovanni
G
Margarino
Carlo
C
Mereu
Armelle
A
Munnia
Marcello
M
Ceppi
Marina
M
Buratti
Raffaella
R
Felletti
Francesca
F
Stea
Roberto
R
Quaglia
Riccardo
R
Puntoni
Emanuela
E
Taioli
Seymour
S
Garte
Stefano
S
Bonassi
D000368:Aged; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis*; D004347:Drug Interactions; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*
D019363:Cytochrome P-450 CYP1A1; D018736:DNA Adducts; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1