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

2.50
Hdl Handle:
http://hdl.handle.net/10146/232192
Title:
Smoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts.
Authors:
Anna, Livia; Kovacs, Katalin; Gyorffy, Erika; Schoket, Bernadette; Nair, Jagadeesan
Abstract:
Tobacco smoke contains many alkylating agents that can react with DNA to produce O(4)-ethylthymidine (O(4)-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 O(4)-etT in smokers' lung; (ii) to explore associations between levels of O(4)-etT and smoking status and (iii) to investigate whether a correlation exists between levels of O(4)-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. O(4)-etT was determined by an immunoenriched (32)P-postlabelling-high-performance liquid chromatography method. Levels of bulky DNA adducts were determined by the nuclease P1 adduct-enriched (32)P-postlabelling. O(4)-etT levels ranged from 0.01 to 3.91 adducts/10(8) 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 O(4)-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 O(4)-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.
Citation:
Mutagenesis 2011, 26 (4):523-527
Journal:
Mutagenesis
Issue Date:
Jul-2011
URI:
http://hdl.handle.net/10146/232192
DOI:
10.1093/mutage/ger011
PubMed ID:
21454326
Additional Links:
http://mutage.oxfordjournals.org/content/26/4/523.long
Type:
Article
Language:
en
ISSN:
1464-3804
Sponsors:
The technical assistance by Mayura Meerang (DKFZ) is gratefully appreciated. L. Anna was the recipient of an Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) Exchange fellowship within ECNIS.
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Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorAnna, Liviaen_GB
dc.contributor.authorKovacs, Katalinen_GB
dc.contributor.authorGyorffy, Erikaen_GB
dc.contributor.authorSchoket, Bernadetteen_GB
dc.contributor.authorNair, Jagadeesanen_GB
dc.date.accessioned2012-07-05T08:21:36Z-
dc.date.available2012-07-05T08:21:36Z-
dc.date.issued2011-07-
dc.identifier.citationMutagenesis 2011, 26 (4):523-527en_GB
dc.identifier.issn1464-3804-
dc.identifier.pmid21454326-
dc.identifier.doi10.1093/mutage/ger011-
dc.identifier.urihttp://hdl.handle.net/10146/232192-
dc.description.abstractTobacco smoke contains many alkylating agents that can react with DNA to produce O(4)-ethylthymidine (O(4)-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 O(4)-etT in smokers' lung; (ii) to explore associations between levels of O(4)-etT and smoking status and (iii) to investigate whether a correlation exists between levels of O(4)-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. O(4)-etT was determined by an immunoenriched (32)P-postlabelling-high-performance liquid chromatography method. Levels of bulky DNA adducts were determined by the nuclease P1 adduct-enriched (32)P-postlabelling. O(4)-etT levels ranged from 0.01 to 3.91 adducts/10(8) 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 O(4)-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 O(4)-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.en_GB
dc.description.sponsorshipThe technical assistance by Mayura Meerang (DKFZ) is gratefully appreciated. L. Anna was the recipient of an Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS) Exchange fellowship within ECNIS.en_GB
dc.language.isoenen
dc.relation.urlhttp://mutage.oxfordjournals.org/content/26/4/523.longen_GB
dc.rightsArchived with thanks to Mutagenesisen_GB
dc.subjectDNA adductsen_GB
dc.subjectSmokingen_GB
dc.subjectO(4)-ethylthymidineen_GB
dc.subjectLungen_GB
dc.subjectHumansen_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshDNA Adducts-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLung-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshSmoking-
dc.subject.meshThymidine-
dc.titleSmoking-related O4-ethylthymidine formation in human lung tissue and comparisons with bulky DNA adducts.en
dc.typeArticleen
dc.identifier.journalMutagenesisen_GB

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