Neurotoxic effect of subacute benzo(a)pyrene exposure on gene and protein expression in Sprague-Dawley rats

Environ Toxicol Pharmacol. 2013 Sep;36(2):648-658. doi: 10.1016/j.etap.2013.06.008. Epub 2013 Jun 28.

Abstract

Benzo(a)pyrene (B[a]P) is an environmental carcinogen that induces tumors in many animal species, but the neurotoxic effects of B[a]P have not been well studied. In the present study, we investigated the effects of subacute exposure to B[a]P in Sprague-Dawley (SD) rats. Male rats received daily injections of either B[a]P (0, 1, 2.5, or 6.25mg/kg, i.p.) or vehicle for 45 days. Exposure to B[a]P affected the behavior of rats in the Morris water maze test. Gene microarray and real-time PCR analyses revealed that exposure to B[a]P affected signal transduction in the rat hippocampus. Protein microarray analysis revealed that altered protein expression played a role in cell death in the functional annotation cluster analysis. Finally, major vault protein was found to display low cDNA and protein expression levels. The present study explored some of the possible mechanisms underlying B[a]P neurotoxicity and provided evidence that B[a]P plays a neurotoxic role in rats.

Keywords: Benz[a]pyrene; Hippocampus; Microarray; Rat; Water maze.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzo(a)pyrene / toxicity*
  • Carcinogens, Environmental / toxicity*
  • Cell Death / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Male
  • Memory / drug effects
  • Motor Activity / drug effects
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / genetics
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / physiopathology
  • Neurotoxicity Syndromes / psychology
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Time Factors
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism

Substances

  • Carcinogens, Environmental
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Benzo(a)pyrene