Toxicogenomic analysis of gender, chemical, and dose effects in livers of TCDD- or aroclor 1254-exposed rats using a multifactor linear model

Toxicological Sciences : an Official Journal of the Society of Toxicology
Jay B SilkworthThomas R Sutter

Abstract

Chronic exposure of Sprague-Dawley (SD) rats to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Aroclor 1254 results in female-selective induction of hepatic tumors. The relative potency of dioxins and polychlorinated biphenyl mixtures, such as Aroclor 1254, is often estimated using the internationally endorsed toxic equivalency (TEQ) approach. Comparing the genome wide changes in gene expression in both genders following exposure to TEQ doses of these chemicals should identify critical sets of early response genes while further defining the concept of the TEQ of halogenated aromatic hydrocarbons. Aroclor 1254 at 0.6, 6.0, and 60 mg/kg body weight and TEQ doses of TCDD (0.3 and 3.0 mug/kg), calculated to match the top two Aroclor 1254 doses, were orally administered to SD rats for three consecutive days. Day 4 gene expression in hepatic tissue was determined using microarrays. A linear mixed-effects statistical model was developed to analyze the data in relation to treatment, gender, and gender * treatment (G*T) interactions. The genes most changed included 54 genes with and 51 genes without a significant model G*T term. The known aryl hydrocarbon receptor (AHR) battery genes (Cyp1a1, Cyp1a2, Cyp1b1, Aldh3a1), and novel ge...Continue Reading

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Citations

Aug 21, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Erik A CarlsonJay B Silkworth
Mar 1, 2009·Journal of Toxicologic Pathology·Naoki KiyosawaTakashi Yamoto
Sep 24, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·G S GadupudiL W Robertson
Oct 2, 2014·Archives of Toxicology·Mirjam M SchaapMirjam Luijten
Apr 12, 2020·Archives of Toxicology·Stephenie D ProkopecRaimo Pohjanvirta
May 9, 2013·Environmental and Molecular Mutagenesis·Sam De CosterNicolas van Larebeke
May 1, 2010·Environmental Toxicology and Pharmacology·Hiroko IshiniwaTsuneo Sekijima

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