Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

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http://hdl.handle.net/10138/203426

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Prokopec , S D , Watson , J D , Lee , J , Pohjanvirta , R & Boutros , P C 2015 , ' Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD ' , Toxicology and Applied Pharmacology , vol. 284 , no. 2 , pp. 188-196 . https://doi.org/10.1016/j.taap.2015.02.012

Title: Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD
Author: Prokopec, Stephenie D.; Watson, John D.; Lee, Jamie; Pohjanvirta, Raimo; Boutros, Paul C.
Contributor: University of Helsinki, Departments of Faculty of Veterinary Medicine
Date: 2015-04
Language: eng
Number of pages: 9
Belongs to series: Toxicology and Applied Pharmacology
ISSN: 0041-008X
URI: http://hdl.handle.net/10138/203426
Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500 mu g/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. (C) 2015 The Authors. Published by Elsevier Inc.
Subject: Aryl hydrocarbon receptor
Computational biology
2,3,7,8-Tetrachlorodibenzo-p-dioxin
TCDD
AH receptor
Sex differences
ARYL-HYDROCARBON RECEPTOR
RESISTANT RAT STRAIN
CONSTITUTIVE ANDROSTANE RECEPTOR
GENE-EXPRESSION PROFILES
SPRAGUE-DAWLEY RATS
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD
NUCLEAR RECEPTOR
MOUSE-LIVER
TOXICOGENOMIC ANALYSIS
CYTOCHROME-P450 GENES
413 Veterinary science
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