Early loss of Fhit in the respiratory tract of rodents exposed to environmental cigarette smoke.

2.50
Hdl Handle:
http://hdl.handle.net/10146/64476
Title:
Early loss of Fhit in the respiratory tract of rodents exposed to environmental cigarette smoke.
Authors:
D'Agostini, Francesco; Izzotti, Alberto; Balansky, Roumen; Zanesi, Nicola; Croce, Carlo M.; De Flora, Silvio
Abstract:
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(F(1)) 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)F(1) 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.
Citation:
Cancer Res. 2006, 66 (7):393639-41
Journal:
Cancer research
Issue Date:
1-Apr-2006
URI:
http://hdl.handle.net/10146/64476
DOI:
10.1158/0008-5472.CAN-05-3666
PubMed ID:
16585223
Additional Links:
http://cancerres.aacrjournals.org/cgi/content/full/66/7/3936
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: Acetylcysteine;Acid Anhydride Hydrolases;Animals;Anticarcinogenic Agents;biosynthesis;Blotting,Western;Bronchi;deficiency;drug effects;Down-Regulation;enzymology;genetics;Hydrolases;Immunohistochemistry;Italy;mechanisms of carcinogenesis;Mice;Neoplasm Proteins;pathology;pharmacology;Proteins;Rats;Rats,Sprague-Dawley;Research;Reverse Transcriptase Polymerase Chain Reaction;Smoke;Sulindac;Tobacco;Tobacco Smoke Pollution.
ISSN:
0008-5472
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorD'Agostini, Francesco-
dc.contributor.authorIzzotti, Alberto-
dc.contributor.authorBalansky, Roumen-
dc.contributor.authorZanesi, Nicola-
dc.contributor.authorCroce, Carlo M.-
dc.contributor.authorDe Flora, Silvio-
dc.date.accessioned2009-04-06T08:13:31Z-
dc.date.available2009-04-06T08:13:31Z-
dc.date.issued2006-04-01-
dc.identifier.citationCancer Res. 2006, 66 (7):393639-41en
dc.identifier.issn0008-5472-
dc.identifier.pmid16585223-
dc.identifier.doi10.1158/0008-5472.CAN-05-3666-
dc.identifier.urihttp://hdl.handle.net/10146/64476-
dc.descriptionKEYWORDS CLASSIFICATION: Acetylcysteine;Acid Anhydride Hydrolases;Animals;Anticarcinogenic Agents;biosynthesis;Blotting,Western;Bronchi;deficiency;drug effects;Down-Regulation;enzymology;genetics;Hydrolases;Immunohistochemistry;Italy;mechanisms of carcinogenesis;Mice;Neoplasm Proteins;pathology;pharmacology;Proteins;Rats;Rats,Sprague-Dawley;Research;Reverse Transcriptase Polymerase Chain Reaction;Smoke;Sulindac;Tobacco;Tobacco Smoke Pollution.en
dc.description.abstractThe 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(F(1)) 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)F(1) 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.en
dc.language.isoenen
dc.relation.urlhttp://cancerres.aacrjournals.org/cgi/content/full/66/7/3936en
dc.subject.meshAcetylcysteine-
dc.subject.meshAcid Anhydride Hydrolases-
dc.subject.meshAnimals-
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshBlotting, Western-
dc.subject.meshBronchi-
dc.subject.meshDown-Regulation-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMice-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshRats-
dc.subject.meshRats, Sprague-Dawley-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSulindac-
dc.subject.meshTobacco Smoke Pollution-
dc.titleEarly loss of Fhit in the respiratory tract of rodents exposed to environmental cigarette smoke.en
dc.typeArticleen
dc.identifier.journalCancer researchen

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