Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung

Alberto Izzotti, Maria Bagnasco, Cristina Cartiglia, Mariagrazia Longobardi, Roumen M. Balansky, Andrea Merello, Ronald A. Lubet, Silvio De Flora

Research output: Contribution to journalArticle

Abstract

Postgenomic methodologies have provided novel tools for evaluating safety and efficacy of cancer chemopreventive agents. We exposed rats to environmental cigarette smoke (ECS) for 28 days, with or without oral administration of N-acetylcysteine (NAC). As assessed by 32P-postlabelling, ECS caused a 10-fold increase of DNA adduct levels, which were significantly reduced by NAC. Of 518 proteins tested by antibody microarray, ECS stimulated 56 activities involved in stress response, protein removal, cell replication, apoptosis, phagocytosis, and immune response. NAC alone did not change the amounts of any protein, whereas it significantly decreased the amounts of 6 ECS-induced proteins. The intensity of expression of 278 related genes, assessed by cDNA microarray, was significantly correlated with protein amounts. These observed molecular alterations, which can be attenuated by NAC, represent in part adaptive responses and in part reflect mechanisms contributing to the pathogenesis of smoke-related diseases, including lung cancer, asthma, chronic bronchitis, and emphysema.

Original languageEnglish
Pages (from-to)1864-1874
Number of pages11
JournalEuropean Journal of Cancer
Volume41
Issue number13
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Antibody microarray
  • Cancer chemoprevention
  • Cigarette smoke
  • DNA adducts
  • Multigene expression
  • N-Acetylcysteine
  • Proteome analysis

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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  • Cite this

    Izzotti, A., Bagnasco, M., Cartiglia, C., Longobardi, M., Balansky, R. M., Merello, A., Lubet, R. A., & De Flora, S. (2005). Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung. European Journal of Cancer, 41(13), 1864-1874. https://doi.org/10.1016/j.ejca.2005.04.011