Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit.
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(F(1)) 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(F(1)) 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.
De Flora
Silvio
S
Department of Health Sciences, University of Genoa, via A. Pastore 1, I-16132 Genoa, Italy. sdf@unige.it
D'Agostini
Francesco
F
Izzotti
Alberto
A
Zanesi
Nicola
N
Croce
Carlo M
CM
Balansky
Roumen
R
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D018736:DNA Adducts; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D018736:DNA Adducts; D009363:Neoplasm Proteins; D012906:Smoke; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase