Differences in gene expression and benzo[a]pyrene-induced DNA adduct formation in the liver of three strains of female mice with identical AhRb2 genotype treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and/or benzo[a]pyrene

J Appl Toxicol. 2008 Aug;28(6):724-33. doi: 10.1002/jat.1331.

Abstract

To search for genes whose products modify aryl hydrocarbon receptor (AhR)-dependent toxicity caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), gene expression profiles in the liver were surveyed using microarrays 24 h after the administration of TCDD to three strains of female mice, BALB/cAnN (BALB), C3H/HeN (C3H) and CBA/JN (CBA) all of identical AhR genotype. The BALB/cAnN strain had a more marked induction of a number of glutathione S-transferase (GST) sub-families, particularly the GSTmicro gene family, compared with the other two strains. To assess the effects of GSTs induction to metabolize carcinogens, TCDD (40 microg kg(-1)) was administered to BALB and CBA strains, followed 24 h later by an i.p. injection of low or high dose of benzo[a]pyrene (B[a]P, 50 or 200 mg kg(-1)). The 32P-postlabelling analysis showed that administration of TCDD alone failed to induce DNA adduct formation in both BALB and CBA strain mouse livers. The low dose of B[a]P alone produced DNA adduct in the liver of both strains to a similar extent. Treatment with TCDD 24 h before the low dose of B[a]P suppressed the formation of B[a]P-induced DNA-adduct more markedly in the BALB strain compared with the CBA strain. Taken together, these findings show that TCDD treatment causes strain-specific alterations in gene expression and B[a]P-induced DNA adduct formation in the liver of female mice of the same AhRb2 genotype. Furthermore, it suggests that TCDD-treated female mice of the BALB strain may have genes whose products modify the toxicity of B[a]P as evidenced by TCDD-induced alterations in B[a]P-DNA adduct formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • DNA Adducts / drug effects*
  • DNA Primers
  • Environmental Pollutants / toxicity*
  • Female
  • Gene Expression / drug effects
  • Genotype
  • Liver / drug effects
  • Liver / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred CBA
  • Oligonucleotide Array Sequence Analysis
  • Polychlorinated Dibenzodioxins / toxicity*
  • Receptors, Aryl Hydrocarbon / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity

Substances

  • DNA Adducts
  • DNA Primers
  • Environmental Pollutants
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Benzo(a)pyrene