Smoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts

Lívia Anna, Katalin Kovács, Erika Gyorffy, B. Schoket, Jagadeesan Nair

Research output: Contribution to journalArticle

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Abstract

Tobacco smoke contains many alkylating agents that can react with DNA to produce O4-ethylthymidine (O4-etT) and several other types of promutagenic base modifications. Our aims were (i) to confirm results of a pilot study (Godschalk, R., Nair, J., Schooten, F. J., Risch, A., Drings, P., Kayser, K., Dienemann, H. and Bartsch, H. (2002) Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking. Carcinogenesis, 23, 2081-2086) on the formation of O4-etT in smokers' lung; (ii) to explore associations between levels of O4-etT and smoking status and (iii) to investigate whether a correlation exists between levels of O4-etT and bulky (polycyclic aromatic hydrocarbons-derived) DNA adducts. Archived DNA samples originated from histologically normal peripheral lung tissues of 64 Hungarian lung cancer patients, who underwent lung resection. O4-etT was determined by an immunoenriched 32P-postlabelling-high-performance liquid chromatography method. Levels of bulky DNA adducts were determined by the nuclease P1 adduct-enriched 32P-postlabelling. O4-etT levels ranged from 0.01 to 3.91 adducts/108 thymidines. In the combined group of subjects who smoked until surgery or gave up smoking at most 1 year before it, the mean level of O4-etT was 1.7-fold (P = 0.015) and of bulky DNA adducts 2.2-fold (P <0.0001) higher than in long-term ex-smokers (LES) and never-smokers (NS) combined. We found no significant correlation between the individual levels of the two DNA adduct types. No dose-response was detected between O 4-etT formation and smoking dose. In one-third of LES, O 4-etT levels were above the 2.0-fold mean level of adducts found in NS, indicating its high persistence. Our results confirm the smoking-related formation of O4-etT in human lung DNA that should be explored as biomarker. Its long persistence in target tissue implicates a role of this potentially miscoding lesion in tobacco smoking-associated cancers.

Original languageEnglish
Pages (from-to)523-527
Number of pages5
JournalMutagenesis
Volume26
Issue number4
DOIs
Publication statusPublished - Jul 2011

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DNA Adducts
Smoking
Tissue
Lung
Tobacco
DNA
Alkylating Agents
Polycyclic Aromatic Hydrocarbons
High performance liquid chromatography
Biomarkers
Smoke
Tobacco Products
Thymidine
Surgery
Tumors
Lung Neoplasms
Neoplasms
Carcinogenesis
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Smoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts. / Anna, Lívia; Kovács, Katalin; Gyorffy, Erika; Schoket, B.; Nair, Jagadeesan.

In: Mutagenesis, Vol. 26, No. 4, 07.2011, p. 523-527.

Research output: Contribution to journalArticle

Anna, Lívia ; Kovács, Katalin ; Gyorffy, Erika ; Schoket, B. ; Nair, Jagadeesan. / Smoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts. In: Mutagenesis. 2011 ; Vol. 26, No. 4. pp. 523-527.
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