Carcinogenesis Advance Access originally published online on March 4, 2004
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Carcinogenesis, Vol. 25, No. 7, 1201-1209,
July 2004
Carcinogenesis vol.25 no.7 © Oxford University Press 2004; all rights reserved.
ARTICLE |
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
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ri2
3
31 National Institute of Environmental Health, József Fodor National Center for Public Health, Budapest, H-1097 Hungary, 2 Béla Johan National Center for Epidemiology, Budapest, H-1529 Hungary, 3 Korányi National Institute of Pulmonology, Budapest, H-1529 Hungary and 4 National Cancer Institute, NIH, Bethesda, MD 20892, USA
5 To whom correspondence should be addressed Email: schoketb{at}okk.antsz.hu
Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogenDNA 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 (±)-7ß, 8
-dihydroxy-9
,10
-epoxy-7,8,9,10-tetrahydrobenzo[a]pyreneDNA chemiluminescence immunoassay (BPDEDNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/108 nucleotides (nt) with mean adduct levels between 2.8 and 11.5 adducts/108 nt. Mean PAHDNA adduct levels were 2.66.2 adducts/108 nt. Significantly higher bulky DNA adduct levels were detected in smokers' lungs as compared with non-smokers' (P < 0.02). PAHDNA 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 BPDEDNA immunoassay (r = 0.27, P = 0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.
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