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


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 toxi

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