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http://dx.doi.org/10.5487/TR.2009.25.2.085

Analysis of Gene Expression in 4,4'-Methylenedianiline-induced Acute Hepatotoxicity  

Oh, Jung-Hwa (Toxicogenomics Team)
Yoon, Hea-Jin (Toxicogenomics Team)
Lim, Jung-Sun (Toxicogenomics Team)
Park, Han-Jin (Toxicogenomics Team)
Cho, Jae-Woo (Clinical Pathology Team)
Kwon, Myung-Sang (Korea Institute of Toxicology, School of Veterinary Medicine, Kangwon National University)
Yoon, Seok-Joo (Toxicogenomics Team)
Publication Information
Toxicological Research / v.25, no.2, 2009 , pp. 85-92 More about this Journal
Abstract
4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.
Keywords
4,4'-Methylenedianiline; Hepatotoxicity; Gene expression profiling;
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