Journal Article

Smoking-related DNA and protein adducts in human tissues

David H. Phillips

in Carcinogenesis

Volume 23, issue 12, pages 1979-2004
Published in print December 2002 | ISSN: 0143-3334
Published online December 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.12.1979
Smoking-related DNA and protein adducts in human tissues

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Tobacco smoking causes not only lung cancer but also cancer of the oral and nasal cavities, oesophagus, larynx, pharynx, pancreas, liver, kidney, stomach, urinary tract and cervix. Tobacco smoke contains many carcinogens that exert their biological effects through interaction of reactive intermediates with DNA to form DNA adducts. The same electrophilic species also react with cellular proteins. The effects of smoking are evident by the detection of elevated levels of carcinogen–DNA adducts in many human tissues and of carcinogen–protein adducts in blood. Components of tobacco smoke also induce oxidative DNA damage. Systemic exposure to tobacco-derived carcinogens is demonstrated by the observation of elevated levels of DNA adducts in tissues not directly exposed to tobacco smoke. For many of these tissues there is epidemiological evidence, varying from comprehensive to preliminary, that smoking is a causative factor in cancer of that site. The effects of passive smoking, which also causes lung cancer in non-smokers, is also evident in elevated levels of protein adducts in exposed non-smokers so exposed, relative to non-exposed non-smokers. This paper reviews the literature on smoking-related DNA and protein adducts in human tissues and shows how such studies have provided mechanistic insight into the epidemiological associations between smoking and cancer.

Keywords: 3-ABP, 3-aminobiphenyl; 4-ABP, 4-aminobiphenyl; BAL, bronchoalveolar lavage; BPDE, benzo[a]pyrene diol-epoxide; CEVal, N-(2-cyanoethyl)valine; DRZ, diagonal radioactive zone; ECD, electrochemical detection; ELISA, enzyme-linked immunosorbent assay; ETS, environmental tobacco smoke; GC-MS, gas chromatography-mass spectrometry; HPB, 4-hydroxy-1-(3-pyridyl)-1-butanone; HOEtVal, N-(2-hydroxyethyl)valine; 7-MedG, 7-methyldeoxyguanosine; 8-oxo-dG, 8-oxo-deoxyguanosine; PAH, polycyclic aromatic hydrocarbon; WBC, white blood cell

Journal Article.  21363 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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