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Title: Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant. TCDD binds and activates the transcription factor aryl hydrocarbon receptor (AHR), leading to adverse biological responses via the alteration of the expression of various AHR target genes. Although small amounts of TCDD are consumed via contaminated daily foodstuffs and environmental exposures, the effects of low-dose TCDD on gene expression in animal tissues have not been clarified, while a number of genes affected by high-dose TCDD were reported. In this study, we comprehensively analyzed gene expression profiles in livers of C57BL/6N mice that were orally administered relatively low doses of TCDD (5, 50, or 500 ng/kg body weight (bw) day{sup -1}) for 18 days. The hepatic TCDD concentrations, measured by gas chromatography-mass spectrometry, were 1.2, 17, and 1063 pg toxicity equivalent quantity (TEQ)/g, respectively. The mRNA level of the cytochrome P450 CYP1A1 was significantly increased by treatment with only TCDD 500 ng/kg bw day{sup -1}. DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the circadian rhythm, cholesterol biosynthesis, fatty acid synthesis, and glucose metabolism in the liver with at all doses of TCDD employed. However, repression of expression of genes involved in energy metabolism was not observedmore » in the livers of Ahr-null mice that were administered the same dose of TCDD. These results indicate that changes in gene expression by TCDD are mediated by AHR and that exposure to low-dose TCDD could affect energy metabolism via alterations of gene expression.« less

Authors:
 [1];  [1];  [2]; ;  [1];  [3];  [4];  [5];  [1];  [6];  [1]
  1. Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)
  2. Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503 (Japan)
  3. Biotechnology Research Laboratory, Towa Environmental Science Co., Ltd., Hiroshima 739-0046 (Japan)
  4. Medical and Environment Technology Co., Ltd., Hiroshima 734-8553 (Japan)
  5. Division of Medicinal Safety Science, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501 (Japan)
  6. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892 (United States)
Publication Date:
OSTI Identifier:
21140836
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 229; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.12.029; PII: S0041-008X(08)00006-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; BIOSYNTHESIS; CARBOXYLIC ACIDS; CHOLESTEROL; DIOXIN; DNA; ENVIRONMENTAL EXPOSURE; GAS CHROMATOGRAPHY; GENES; GLUCOSE; HYDROCARBONS; LIVER; MASS SPECTROSCOPY; METABOLISM; MICE; POLYMERASE CHAIN REACTION; RECEPTORS; TOXICITY; TRANSCRIPTION FACTORS

Citation Formats

Sato, Shoko, Shirakawa, Hitoshi, Tomita, Shuhei, Ohsaki, Yusuke, Haketa, Keiichi, Tooi, Osamu, Santo, Noriaki, Research Center for Green Science, Fukuyama University, Fukuyama 729-0292, Tohkin, Masahiro, Furukawa, Yuji, Gonzalez, Frank J, and Komai, Michio. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.12.029.
Sato, Shoko, Shirakawa, Hitoshi, Tomita, Shuhei, Ohsaki, Yusuke, Haketa, Keiichi, Tooi, Osamu, Santo, Noriaki, Research Center for Green Science, Fukuyama University, Fukuyama 729-0292, Tohkin, Masahiro, Furukawa, Yuji, Gonzalez, Frank J, & Komai, Michio. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver. United States. https://doi.org/10.1016/j.taap.2007.12.029
Sato, Shoko, Shirakawa, Hitoshi, Tomita, Shuhei, Ohsaki, Yusuke, Haketa, Keiichi, Tooi, Osamu, Santo, Noriaki, Research Center for Green Science, Fukuyama University, Fukuyama 729-0292, Tohkin, Masahiro, Furukawa, Yuji, Gonzalez, Frank J, and Komai, Michio. 2008. "Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver". United States. https://doi.org/10.1016/j.taap.2007.12.029.
@article{osti_21140836,
title = {Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver},
author = {Sato, Shoko and Shirakawa, Hitoshi and Tomita, Shuhei and Ohsaki, Yusuke and Haketa, Keiichi and Tooi, Osamu and Santo, Noriaki and Research Center for Green Science, Fukuyama University, Fukuyama 729-0292 and Tohkin, Masahiro and Furukawa, Yuji and Gonzalez, Frank J and Komai, Michio},
abstractNote = {2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant. TCDD binds and activates the transcription factor aryl hydrocarbon receptor (AHR), leading to adverse biological responses via the alteration of the expression of various AHR target genes. Although small amounts of TCDD are consumed via contaminated daily foodstuffs and environmental exposures, the effects of low-dose TCDD on gene expression in animal tissues have not been clarified, while a number of genes affected by high-dose TCDD were reported. In this study, we comprehensively analyzed gene expression profiles in livers of C57BL/6N mice that were orally administered relatively low doses of TCDD (5, 50, or 500 ng/kg body weight (bw) day{sup -1}) for 18 days. The hepatic TCDD concentrations, measured by gas chromatography-mass spectrometry, were 1.2, 17, and 1063 pg toxicity equivalent quantity (TEQ)/g, respectively. The mRNA level of the cytochrome P450 CYP1A1 was significantly increased by treatment with only TCDD 500 ng/kg bw day{sup -1}. DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the circadian rhythm, cholesterol biosynthesis, fatty acid synthesis, and glucose metabolism in the liver with at all doses of TCDD employed. However, repression of expression of genes involved in energy metabolism was not observed in the livers of Ahr-null mice that were administered the same dose of TCDD. These results indicate that changes in gene expression by TCDD are mediated by AHR and that exposure to low-dose TCDD could affect energy metabolism via alterations of gene expression.},
doi = {10.1016/j.taap.2007.12.029},
url = {https://www.osti.gov/biblio/21140836}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 229,
place = {United States},
year = {Thu May 15 00:00:00 EDT 2008},
month = {Thu May 15 00:00:00 EDT 2008}
}