Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 gene

Courtney E. Hill, Alessandra A. Affatato, Kevin J. Wolfe, Mirtha S. Lopez, Csilla K. Hallberg, Donatella Canistro, Sherif Abdel-Rahman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The rapid increase in adenocarcinoma of the lung and mortality amongst women strongly suggests that gender differences exist in sensitivity to certain tobacco carcinogens. In the current study, we performed the mutagen-sensitivity assay, with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK), to test the hypothesis that women are more sensitive to the genotoxic effects of NNK than men. Chromosome aberration (CA) frequencies in peripheral blood lymphocytes (PBLs) from 99 patients were evaluated before and after in vitro exposure to NNK. Because the Thr241Met polymorphism in the DNA-repair gene XRCC3 is associated with increased risk of tobacco-related cancers, especially among women, we also tested the hypothesis that individuals who inherit the homozygous variant 241Met allele are more sensitive to the genotoxic effects of NNK. CA frequency was significantly higher 1 hr after NNK treatment in women, compared with men (P = 0.02). When smoking and gender were considered together, a significant interaction was observed. PBLs from female smokers had significantly higher frequencies of NNK-induced CA, compared with female nonsmokers 1 hr after treatment (P = 0.02). We observed no overall effect of the Thr241Met polymorphism on NNK-induced CA in men, women, smokers, or nonsmokers. Overall, our data indicate that women are more sensitive to the genotoxic effects of NNK than men. Because in past years smoking among women has increased, and in view of the close correlation between NNK exposure and adenocarcinoma of the lung, our data provide a plausible explanation for the recent increase in the incidence of this cancer among women.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalEnvironmental and Molecular Mutagenesis
Volume46
Issue number1
DOIs
StatePublished - Jul 2005

Fingerprint

Nitrosamines
Tobacco
Chromosomes
Polymorphism
Aberrations
tobacco
gender
polymorphism
Genes
damage
Lymphocytes
gene
Chromosome Aberrations
chromosome
Blood
Mutagens
smoking
Carcinogens
cancer
Assays

Keywords

  • DNA repair
  • Mutagen-sensitivity
  • NNK
  • Polymorphism
  • Smoking
  • XRCC3

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 gene. / Hill, Courtney E.; Affatato, Alessandra A.; Wolfe, Kevin J.; Lopez, Mirtha S.; Hallberg, Csilla K.; Canistro, Donatella; Abdel-Rahman, Sherif.

In: Environmental and Molecular Mutagenesis, Vol. 46, No. 1, 07.2005, p. 22-29.

Research output: Contribution to journalArticle

Hill, Courtney E. ; Affatato, Alessandra A. ; Wolfe, Kevin J. ; Lopez, Mirtha S. ; Hallberg, Csilla K. ; Canistro, Donatella ; Abdel-Rahman, Sherif. / Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 gene. In: Environmental and Molecular Mutagenesis. 2005 ; Vol. 46, No. 1. pp. 22-29.
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