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Pharmacological modulation of genome and proteome alterations in mice treated with the endocrine disruptor bisphenol

Alberto Izzotti1, Mariagrazia Longobardi, Cristina Cartiglia

  • 1Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy.

Current Cancer Drug Targets
|January 22, 2010
PubMed

Insights

The chemopreventive agent phenethyl isothiocyanate (PEITC) partially reduced bisphenol A (BPA)-induced DNA damage in mice, while budesonide (BUD) was ineffective. Proteome analysis revealed BPA altered key cellular processes, and neither agent fully restored normal function.

Area of Science:

  • Endocrinology
  • Toxicology
  • Molecular Biology

Background:

  • Bisphenol A (BPA) is a widespread environmental endocrine disruptor with known genotoxicity.
  • Previous studies showed BPA induces DNA adducts in mouse liver and mammary tissue.
  • Chemopreventive agents are explored for mitigating BPA's adverse effects.

Purpose of the Study:

  • To evaluate the efficacy of budesonide (BUD) and phenethyl isothiocyanate (PEITC) in modulating BPA-induced DNA adducts and proteome alterations.
  • To assess the potential of proteome analysis for predicting chemopreventive agent efficacy and adverse effects.

Main Methods:

  • Swiss ICR (CD-1) mice were administered BPA orally and either BUD or PEITC via diet for 8 days.
  • DNA adducts were quantified using (32)P postlabeling.
  • Proteome alterations were analyzed using antibody microarrays targeting 656 proteins.

Main Results:

  • BPA induced similar DNA adduct formation in liver and mammary tissues.
  • BPA dysregulated 13 proteins in mammary tissue, including estrogen receptor-beta, affecting cell proliferation, apoptosis, and stress response.
  • PEITC significantly inhibited BPA-induced DNA adducts at the highest dose; BUD showed no effect.
  • Both agents modulated BPA-induced proteome changes, but neither fully restored physiological conditions.

Conclusions:

  • PEITC demonstrated partial chemopreventive activity against BPA-induced genotoxicity.
  • Proteome analysis is a sensitive tool for evaluating both the protective and adverse effects of chemopreventive agents in vivo.
  • Neither BUD nor PEITC fully reversed BPA-induced molecular disruptions in the tested model.

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