Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells.
The presence of carcinogen-DNA adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5'-32P-labelled deoxyribonucleoside 3',5'-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/- 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 adducts/10(8) nucleotides, respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P-post-labelling. Adduct levels in the smokers' samples were not significantly different from levels in the non-smokers' samples (2.53 +/- 1.31 and 2.12 +/- 1.44 adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.
Phillips
D H
DH
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Schoket
B
B
Hewer
A
A
Bailey
E
E
Kostic
S
S
Vincze
I
I
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000187:drug effects*; D003367:Cotinine / Q000097:blood; D004247:DNA / Q000032:analysis / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008175:Lung Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012907:Smoking / Q000235:genetics*
D004247:DNA; D003367:Cotinine