Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit

Silvio De Flora, Francesco D'Agostini, Alberto Izzotti, Nicola Zanesi, Carlo M. Croce, Roumen Balansky

Research output: Contribution to journalArticle

Abstract

Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke. We compared the induction of a variety of molecular and cytogenetical alterations in B6-129(F1) mice, either wild type or Fhit+/-, after whole-body exposure to environmental cigarette smoke (ECS) for 15 consecutive days. Both mouse genotypes responded to ECS with a loss of Fhit protein in the bronchial epithelium, accompanied by induction of apoptosis and stimulation of cell proliferation. ECS induced formation of bulky DNA adducts in whole lung. In addition, ECS caused cytogenetical damage both in the respiratory tract and at a systemic level, as shown by a significant increase of micronucleus frequency in pulmonary alveolar macrophages, bone marrow polychromatic erythrocytes, and peripheral blood normochromatic erythrocytes of both wild-type and Fhit +/- mice. These results are compared with those generated in other species, strains, and genotypes of rodents exposed to ECS that we investigated previously. Although the loss of Fhit protein in the bronchial epithelium of ECS-exposed B6-129(F1) mice provides further evidence that the Fhit gene is an early molecular target for ECS, heterozygosity for Fhit does not seem to confer an increased susceptibility of mice in terms of the investigated early biomarkers.

Original languageEnglish
Pages (from-to)1001-1006
Number of pages6
JournalCancer Research
Volume67
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

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Smoke
Tobacco Products
129 Strain Mouse
Alveolar Macrophages
Epithelium
Erythrocytes
Genotype
DNA Adducts
Environmental Exposure
Respiratory System
Genes
Rodentia
Proteins
Animal Models
Biomarkers
Bone Marrow
Cell Proliferation
Apoptosis
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit. / De Flora, Silvio; D'Agostini, Francesco; Izzotti, Alberto; Zanesi, Nicola; Croce, Carlo M.; Balansky, Roumen.

In: Cancer Research, Vol. 67, No. 3, 01.02.2007, p. 1001-1006.

Research output: Contribution to journalArticle

De Flora, Silvio ; D'Agostini, Francesco ; Izzotti, Alberto ; Zanesi, Nicola ; Croce, Carlo M. ; Balansky, Roumen. / Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit. In: Cancer Research. 2007 ; Vol. 67, No. 3. pp. 1001-1006.
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