This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D'Agostini, F. Articles by De Flora, S. Search for Related Content PubMed PubMed Citation Articles by D'Agostini, F. Articles by De Flora, S. Related Collections Oncogenesis Oncogenesis: Animal Models

Early Loss of Fhit in the Respiratory Tract of Rodents Exposed to Environmental Cigarette Smoke

¹ Department of Health Sciences, University of Genoa, Genoa, Italy and ² Comprehensive Cancer Center, Ohio State University, Columbus, Ohio

Requests for reprints: Silvio De Flora, Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy. Phone: 39-10-353-8500; Fax: 39-10-353-8504; E-mail: sdf{at}unige.it.

The Fhit gene, encompassing the most active common human chromosomal fragile region, FRA3B, has been shown to act as a tumor suppressor. Several studies have shown significant Fhit alterations or Fhit protein loss in lung cancers from smokers compared with lung cancers from nonsmokers. To evaluate the role of Fhit under controlled experimental conditions, we exposed rodents to environmental cigarette smoke (ECS) and evaluated Fhit expression or Fhit protein in the respiratory tract. After 14 days of exposure to ECS, loss of Fhit protein in the bronchial/bronchiolar epithelium affected half of the tested B6-129(F₁) mice, either wild type or Fhit^+/–. After 28 days, it affected the vast majority of the tested SKH-1 hairless mice and of A/J mice and all (UL53-3 x A/J)F₁ mice, either wild type or P53^+/–. In Sprague-Dawley rats, exposure to ECS for up to 30 days caused a time-dependent loss of Fhit in pulmonary alveolar macrophages. Moreover, ECS down-regulated Fhit expression and significantly decreased Fhit protein in the rat bronchial epithelium. The oral administration of N-acetylcysteine attenuated the ECS-related loss of Fhit, whereas oltipraz, 5,6-benzoflavone, phenethyl isothiocyanate, and indole 3-carbinol, and their combinations had no significant effect. Parallel studies evaluated a variety of molecular, biochemical, and cytogenetic alterations in the respiratory tract of the same animals. In conclusion, there is unequivocal evidence that Fhit is an early, critical target in smoke-related lung carcinogenesis in rodents, and that certain chemopreventive agents can attenuate the occurrence of this gene alteration. (Cancer Res 2006; 66(7): 3936-41)

This article has been cited by other articles:

				S. De Flora, F. D'Agostini, A. Izzotti, N. Zanesi, C. M. Croce, and R. Balansky Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for Fhit Cancer Res., February 1, 2007; 67(3): 1001 - 1006. [Abstract] [Full Text] [PDF]

				V. Donati, G. Fontanini, M. Dell'Omodarme, M. C. Prati, S. Nuti, M. Lucchi, A. Mussi, M. Fabbri, F. Basolo, C. M. Croce, et al. WWOX Expression in Different Histologic Types and Subtypes of Non-Small Cell Lung Cancer Clin. Cancer Res., February 1, 2007; 13(3): 884 - 891. [Abstract] [Full Text] [PDF]

				R. Balansky, F. D'Agostini, G. Ganchev, A. Izzotti, B. Di Marco, R. A. Lubet, N. Zanesi, C. M. Croce, and S. De Flora Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N-acetylcysteine PNAS, May 16, 2006; 103(20): 7823 - 7828. [Abstract] [Full Text] [PDF]