Modulation of multigene expression and proteome profiles by chemopreventive agents

Alberto Izzotti, Maria Bagnasco, Cristina Cartiglia, Mariagrazia Longobardi, Anna Camoirano, Elena Tampa, Ronald A. Lubet, Silvio De Flora

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Analysis of transcriptome and proteome profiles by microarray technologies provides a formidable, new tool in cancer chemoprevention research. An ideal chemopreventive agent should not excessively alter per se the basal make-up of multigene expression and protein synthesis and should at the same time be able to attenuate alterations induced by risk factors. In order to validate this working hypothesis, we previously performed a series of studies in animal models using the thiol N-acetyl-l-cysteine (NAC) and the nonsteroidal antiinflammatory drug sulindac. We report herein the results of new studies evaluating modulation of DNA adduct levels and expression of 4858 genes in lung and liver of Sprague-Dawley rats, either unexposed or exposed to environmental cigarette smoke (ECS). The tested chemopreventive agents included NAC, oltipraz (OPZ), 5,6-benzoflavone (5,6-BF), phenethyl isothiocyanate (PEITC), and indole 3-carbinol (I3C). Combinations of OPZ with NAC and of PEITC with I3C were also assayed. Excepting OPZ, all treatments inhibited by at least 50% the formation of bulky DNA adducts in the lung of ECS-exposed rats. Hierarchical cluster analysis and principal component analysis allowed us to classify the agents according to their influence on basal gene expression and their ability to attenuate ECS-induced transcriptome alterations. PEITC and I3C were the most effective but the least safe agents. 5,6-BF displayed intermediate patterns. OPZ was poorly effective in lung and considerably altered the basal gene expression in liver. NAC had a medium efficacy and was the safest agent, as also supported by the analysis of 518 proteins in rat lung.

Original languageEnglish
Pages (from-to)212-223
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume591
Issue number1-2
DOIs
Publication statusPublished - Dec 11 2005

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Proteome
Cysteine
Smoke
Tobacco Products
beta-Naphthoflavone
Lung
DNA Adducts
Transcriptome
Gene Expression
Sulindac
Liver
Chemoprevention
Principal Component Analysis
Sulfhydryl Compounds
Sprague Dawley Rats
Cluster Analysis
Proteins
Anti-Inflammatory Agents
Animal Models
Technology

Keywords

  • 5,6-Benzoflavone
  • Cancer chemoprevention
  • cDNA array
  • DNA adducts
  • Environmental cigarette smoke
  • Indole 3-carbinol
  • N-Acetylcysteine
  • Oltipraz
  • Phenethyl isothiocyanate
  • Proteome

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis

Cite this

Modulation of multigene expression and proteome profiles by chemopreventive agents. / Izzotti, Alberto; Bagnasco, Maria; Cartiglia, Cristina; Longobardi, Mariagrazia; Camoirano, Anna; Tampa, Elena; Lubet, Ronald A.; De Flora, Silvio.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 591, No. 1-2, 11.12.2005, p. 212-223.

Research output: Contribution to journalArticle

Izzotti, Alberto ; Bagnasco, Maria ; Cartiglia, Cristina ; Longobardi, Mariagrazia ; Camoirano, Anna ; Tampa, Elena ; Lubet, Ronald A. ; De Flora, Silvio. / Modulation of multigene expression and proteome profiles by chemopreventive agents. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2005 ; Vol. 591, No. 1-2. pp. 212-223.
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