Induction and modulation of lung tumors: Genomic and transcriptional alterations in cigarette smoke-exposed mice

Silvio De Flora, Alberto Izzotti, Francesco D'Agostini, Carlo Bennicelli, Ming You, Ronald A. Lubet, Roumen M. Balansky

Research output: Contribution to journalArticle

Abstract

Cigarette smoke plays a major role in the epidemiology of lung cancer, and smoke components have extensively been investigated in carcinogenicity and chemoprevention studies in experimental animals. However, it is much more difficult to reproduce the tumongenicity of the whole complex mixture in pre-clinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transcriptional alterations in smoke-exposed mice. The authors were successful in inducing lung tumors in 4 strains of mice exposed whole-body to environmental cigarette smoke, including Swiss albino, A/J, SKH-1 hairless, and p53 mutant (UL53-3 × A/J)F1 mice. However, the tumorigenic response was rather weak in all strains. Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow, and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2′-deoxyguanosine; multigene expression; and thiobarbituric acid-reactive aldehydes in whole lung and several other organs. Smoke-induced genomic and transcriptional alterations were suitable for evaluating their modulation by chemopreventive agents, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.

Original languageEnglish
Pages (from-to)19-35
Number of pages17
JournalExperimental Lung Research
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2005

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Keywords

  • Chemoprevention
  • Cigarette smoke
  • Genomic alterations
  • Lung tumors
  • Murine models
  • Transcriptional alterations

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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