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Time- and Dose-based Gene Expression Profiles Produced by a Bile-duct-damaging Chemical, 4,4'-methylene Dianiline, in Mouse Liver in an Acute Phase

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Authors
Kwon, Sun-Bom; Park, Joon-Suk; Yi, Jung-Yeon; Hwang, Jae-Wong; Kim, Mingoo; Lee, Mi-Ock; Lee, Byung-Hoon; Kim, Hyung-Lae; Kim, Ju Han; Chung, Heekyoung; Kong, Gu; Kang, Kyung-Sun; Yoon, Byung-Il
Issue Date
2008-07-22
Publisher
Taylor & Francis
Citation
Toxicol Pathol 36, 660-73
Keywords
acute liver toxicity4,4’-methylene dianilinemousetoxicogenomics
Abstract
A toxicogenomics study was performed in the mouse liver after treatment of a bile-duct–damaging chemical, 4,4’-methylene dianiline (MDA), across
multiple doses and sampling times in an acute phase using the AB Expression Array System. Imprinting control region (ICR) mice were given a single
oral administration of a low (10 mg/kg b.w.) or high (100 mg/kg b.w.) dose of MDA. Mice were sacrificed six, twenty-four, and seventy-two hours after
treatment for serum chemistry, histopathology, and mRNA preparation from liver samples. Treatment with MDA increased liver-toxicity–related
enzymes in blood and induced bile-duct cell injury, followed by regeneration. To explore potential biomarker gene profiles, the altered genes were
categorized into four expression patterns depending on dose and time. Numerous functionally defined and unclassified genes in each category were
up- or down-regulated throughout the period from cellular injury to the recovery phase, verified by RT-PCR. Many genes associated with liver toxicity
and diseases belonged to one of these categories. The chemokine-mediated Th1 pathway was implicated in the inflammatory process. The genes
associated with oxidative stress, apoptosis, and cell-cycle regulation were also dynamically responsive to MDA treatment. The Wnt/β-catenin
signaling pathway was likely responsible for the reconstitution process of the MDA-injured liver.
ISSN
0192-6233 (print)
1533-1601 (online)
Language
English
URI
http://hdl.handle.net/10371/8285
DOI
https://doi.org/10.1177/0192623308320272
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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