Covalent DNA damage in tissues of cigarette smokers as determined by 32P-postlabeling assay.
Covalent DNA addition products (adducts) formed by the reaction of chemical carcinogens or their metabolites with DNA are critically involved in the initiation of chemical carcinogenesis and may serve as molecular markers and dosimeters for environmental carcinogen exposures. Using a highly sensitive 32P-postlabeling assay for DNA adduct analysis, we studied DNA damage elicited by cigarette smoke in tissues of smokers. A multitude of characteristic smoking-induced, presumably aromatic DNA adducts were found to occur in a dose- and time-dependent manner in the lung, bronchus, and larynx of smokers with cancer of these organs and to decline only slowly after cessation of smoking. Low levels of adducts appeared to persist for up to 14 years in the lungs of exsmokers with high previous exposures. These results corroborate data of epidemiological studies showing that the lung cancer risk and mortality of smokers increase with the intensity and duration of smoking and decline only slowly after cessation of smoking. Tissue distribution studies in autopsy samples revealed the presence of smoking-associated DNA lesions also in the kidney, bladder, esophagus, heart, ascending aorta, and liver. The most extensive DNA damage was found in lung and heart, i.e., 1 aromatic adduct in about 10(7) DNA nucleotides. Our results suggest that cigarette smoking-induced DNA adduct formation is causally related to cancer in the target organs.
Randerath
E
E
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Miller
R H
RH
Mittal
D
D
Avitts
T A
TA
Dunsford
H A
HA
Randerath
K
K
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000032:analysis; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D004825:Epiglottis / Q000032:analysis; D004947:Esophagus / Q000032:analysis; D005260:Female; D006801:Humans; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000032:analysis; D010761:Phosphorus Radioisotopes; D012907:Smoking / Q000378:metabolism*
D010761:Phosphorus Radioisotopes; D004247:DNA