DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay.

Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by 32P-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/10(8) nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/10(8) nt. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/10(8) nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAH-DNA adduct levels appeared higher in the lungs of smokers compared with non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared with normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r = 0.55, P = 0.023). In lung tumour DNA samples there was a weak correlation between values obtained by 32P-postlabelling and by the BPDE-DNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.

[1]  F. Perera,et al.  Postlabeling and immunoassay analysis of polycyclic aromatic hydrocarbons--adducts of deoxyribonucleic acid in white blood cells of foundry workers. , 1990, Scandinavian journal of work, environment & health.

[2]  D. Phillips,et al.  Standardization and validation of DNA adduct postlabelling methods: report of interlaboratory trials and production of recommended protocols. , 1999, Mutagenesis.

[3]  J Verhaert,et al.  Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers. , 1998, Carcinogenesis.

[4]  S. J. Culp,et al.  Immunochemical, 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA adducts in human peripheral lung in relation to metabolic activation pathways involving pulmonary N-oxidation, conjugation, and peroxidation. , 1997, Mutation research.

[5]  S. Hecht,et al.  Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using structure-specific methods. , 2003, Mutation research.

[6]  J. Jang,et al.  Benzo[a]pyrene diol-epoxide-I-DNA and oxidative DNA adducts associated with gastric adenocarcinoma. , 1998, Cancer letters.

[7]  B. Schoket.  DNA damage in humans exposed to environmental and dietary polycyclic aromatic hydrocarbons. , 1999, Mutation research.

[8]  R. Sinha,et al.  Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring. , 2002, Carcinogenesis.

[9]  N. van Zandwijk,et al.  Polycyclic aromatic hydrocarbon--DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung. , 1992, Carcinogenesis.

[10]  H. Thomas,et al.  DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma , 2003, Gut.

[11]  K. Hemminki,et al.  DNA adducts in human nasal mucosa and white blood cells from smokers and non-smokers. , 1997, Carcinogenesis.

[12]  J. Wiencke.  DNA adduct burden and tobacco carcinogenesis , 2002, Oncogene.

[13]  Richard Doll,et al.  The causes of cancer. , 2001, Revue d'epidemiologie et de sante publique.

[14]  D. Nebert,et al.  Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. , 1982, Pharmacological reviews.

[15]  L. V. van't Veer,et al.  32P-postlabelling of aromatic DNA adducts in white blood cells and alveolar macrophages of smokers: saturation at high exposures. , 1997, Mutation research.

[16]  R Mustonen,et al.  Smoking-related DNA adducts: 32P-postlabeling analysis of 7-methylguanine in human bronchial and lymphocyte DNA. , 1993, Carcinogenesis.

[17]  E C Miller,et al.  Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules , 1981, Cancer.

[18]  F. Beland,et al.  DNA adduct measurements and tumor incidence during chronic carcinogen exposure in animal models: implications for DNA adduct-based human cancer risk assessment. , 1992, Chemical research in toxicology.

[19]  P Vineis,et al.  XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. , 2001, Carcinogenesis.

[20]  R. Santella,et al.  Carcinogen macromolecular adducts and their measurement. , 2000, Carcinogenesis.

[21]  H. Bartsch,et al.  Polycyclic aromatic hydrocarbon-DNA adducts in humans: relevance as biomarkers for exposure and cancer risk. , 1998, Mutation research.

[22]  F J van Schooten,et al.  Aromatic DNA adducts in human white blood cells and skin after dermal application of coal tar. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[23]  D. Phillips,et al.  Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells , 1990, International journal of cancer.

[24]  E. Mark,et al.  Polymorphisms in the Dna Repair Genes Xrcc1 and Ercc2 and Biomarkers of Dna Damage in Human Blood Mononuclear Cells Cross-complementing Group 1) than in 399arg/arg Carriers of Breaks following Base Excision Repair (ber) Resulting From , 2022 .

[25]  D. Phillips,et al.  Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar. , 1990, The Journal of investigative dermatology.

[26]  E. Mark,et al.  Early age at smoking initiation and tobacco carcinogen DNA damage in the lung. , 1999, Journal of the National Cancer Institute.

[27]  L. Möller,et al.  Analysis of aromatic DNA adducts in laryngeal biopsies , 2000, European Archives of Oto-Rhino-Laryngology.

[28]  F P Perera,et al.  A molecular epidemiological case-control study of lung cancer. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  C. Harris,et al.  Derivative fluorescence spectral analysis of polycyclic aromatic hydrocarbon-DNA adducts in human placenta. , 1989, Chemical research in toxicology.

[30]  H. Dienemann,et al.  Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking. , 2002, Carcinogenesis.

[31]  DNA adducts in peripheral blood lymphocytes from aluminum production plant workers determined by 32P-postlabeling and enzyme-linked immunosorbent assay. , 1993, Environmental health perspectives.

[32]  K. Hemminki,et al.  Aromatic DNA adducts in larynx biopsies and leukocytes. , 1994, Carcinogenesis.

[33]  D. Phillips,et al.  Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI and GSTM1 genotypes in lung patients. , 1998, Carcinogenesis.

[34]  A. Neugut,et al.  Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke. , 2003, Carcinogenesis.

[35]  D. Phillips.  Smoking-related DNA and protein adducts in human tissues. , 2002, Carcinogenesis.

[36]  K. Hemminki,et al.  DNA adducts in lymphocytes and granulocytes of smokers and nonsmokers detected by the 32P-postlabelling assay. , 1991, Carcinogenesis.

[37]  J. Lewtas,et al.  Air pollution exposure-DNA adduct dosimetry in humans and rodents: evidence for non-linearity at high doses. , 1997, Mutation research.

[38]  W. Tsai,et al.  Polycyclic aromatic hydrocarbon‐DNA adducts in liver tissues of hepatocellular carcinoma patients and controls , 2002, International journal of cancer.