Journal Article

Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking*

R. Godschalk, J. Nair, F.J. van Schooten, A. Risch, P. Drings, K. Kayser, H. Dienemann and H. Bartsch

in Carcinogenesis

Volume 23, issue 12, pages 2081-2086
Published in print December 2002 | ISSN: 0143-3334
Published online December 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.12.2081
Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking*

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Cigarette smokers inhale a broad range of carcinogens derived from tobacco and its pyrolysis products, including free radicals, which induce oxidative stress and subsequent lipid peroxidation (LPO). Miscoding carcinogen–DNA adducts are formed by cigarette smoke constituents and are thought to initiate lung carcinogenesis. The presence of various types of DNA damage was therefore analyzed in tumor adjacent uninvolved lung tissues of 13 smoking and 11 non-smoking operated lung cancer patients. O4-ethylthymidine (O4etT), 1,N6-ethenodeoxyadenosine (εdA) and 3,N4-ethenodeoxycytidine (εdC) were determined by immuno-enriched 32P-postlabeling. Polycyclic aromatic hydrocarbon (PAH)–DNA adducts were measured as diagonal radioactive zones after nuclease P1 enriched 32P-postlabeling. Mean O4etT and PAH–DNA adduct levels were higher in lung DNA of smokers than of non-smokers (O4etT/108 thymidine: 3.8 versus 1.6, P < 0.01; PAH–DNA adducts/108 nucleotides: 11.2 versus 2.2, P < 0.01). Pulmonary etheno–DNA adduct levels did not differ between smokers and non-smokers, but large inter-individual variations were observed (80- and 250-fold differences for εdA and εdC, respectively). As all smokers (except one) refrained from smoking at least for 1 week before surgery, our results demonstrate the persistence of O4etT and PAH–DNA adducts in human lung. A positive correlation obtained between O4etT and PAH–DNA adducts (R = 0.65, P < 0.01) suggests that both adducts are formed from cigarette smoke as the main exposure source. We conclude that in addition to the DNA adducts derived from PAH and tobacco-specific nitrosamines, miscoding O4etT lesions are formed by cigarette smoke that contribute to the increased genomic instability and increased lung cancer risk in smokers.

Keywords: BPDE, benzo[a]pyrene-diol epoxide; εdA, 1,N6-ethenodeoxyadenosine; εdC, 3,N4-ethenodeoxycytidine; LPO, lipid peroxidation; NDEA, N-nitrosodiethylamine; O4etT, O4-ethylthymidine; PAH, polycyclic aromatic hydrocarbons; PEI, polyethyleneimine

Journal Article.  4754 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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