Browse > Article

Gene Expression Analysis of Methotrexate-induced Hepatotoxicity between in vitro and in vivo  

Jung, Jin-Wook (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Kim, Seung-Jun (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Kim, Jun-Sup (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Park, Joon-Suk (Department of Veterinary Public Health, College of Veterinary Medicine)
Yeom, Hye-Jung (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Kim, Ji-Hoon (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Her, Young-Sun (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Lee, Yong-Soon (Department of Veterinary Public Health, College of Veterinary Medicine)
Kang, Jong-Soo (Research Institute. Shin-Won Scientific Co., Ltd.)
Lee, Gyoung-Jae (Research Institute. Shin-Won Scientific Co., Ltd.)
Kim, Yang-Seok (Bioinformatics Unit, ISTECH Inc.)
Kang, Kyung-Sun (Department of Veterinary Public Health, College of Veterinary Medicine)
Hwang, Seung-Yong (Division of Molecular and Life Science, Hanyang University & Genocheck Co., Ltd)
Publication Information
Molecular & Cellular Toxicology / v.1, no.4, 2005 , pp. 256-261 More about this Journal
Abstract
The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.
Keywords
Methotrexate; toxicogenomics; gene expression; rat liver; epithelial cells;
Citations & Related Records

Times Cited By Web Of Science : 2  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Hamadeh, H.K. et al. Gene expression analysis reveals chemical-specific profiles. Toxicol. Sci. 67, 219 -231 (2002)   DOI
2 Hytiroglou, P., Tobias, H., Saxena, R., Abramidou, M., Papadimitriou, C.S. & Theise, N.D. The canals of hering might represent a target of methotrexate hepatic toxicity. Am. J. Clin. Pathol. 121, 324-329 (2004)   DOI   ScienceOn
3 DeRisi J. et al. Trent J.M. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 14, 457-460 (1996)   DOI   ScienceOn
4 Jin, W.J. et al. Gene Expression Analysis of Peroxi- some Proliferators- and Phenytoin-Induced Hepatotoxicity Using cDNA Microarray. J. Vet. Med. Sci. 66, 1329-1333 (2004)   DOI   ScienceOn
5 Sur, P., Matsuo, Y., Otani, T. & Minowada, J. Modulation of methotrexate cytotoxicity with natural interferon upon human leukemia cell line HL-60. Oncology. 48, 469-473 (1991)   DOI   ScienceOn
6 Yoshida, M. et al. Methotrexate suppresses inflammatory agonist induced interleukin 6 synthesis in osteoblasts. J. Rheumatol. 32, 787-795 (2005)   DOI
7 Gyoung, J.L. et al. cDNA microarray gene expression analysis and toxicological phenotype for anticancer drug. J. Vet. Med. Sci. 66, 1339-1343 (2004)   DOI   ScienceOn
8 Guo, J., Chu, M., Abbeyquaye, T. & Chen, C.Y. Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation. J. Biol. Chem. 280, 30422-30431 (2005)   DOI   ScienceOn
9 Fleck, C., Wennek-Klose, J., Wange, J. & Oelschlager, H. Effects and toxicity of new fomocaine derivatives and of 2-hydroxypropyl-beta-cyclodextrin inclusion compounds in rats. Arzneimittelforschung. 54, 265- 274 (2004)
10 Couret, M., Combe, B., Reme, T. & Sany, J. Production of interleukin 2 and interferon-gamma in rheumatoid polyarthritis during a longitudinal study conducted on patients treated with methotrexate. Rev Rhum. Mal. Osteoartic. 57, 641-645 (1990)
11 Wilbert, F.M. & Kemmelmeier, C. Identification of deoxynivalenol, 3-acetyldeoxynivalenol, and zearalenone in galactose oxidase-producing isolates of Fusarium graminearum. J. Basic Microbiol. 43, 148-157 (2003)   DOI   ScienceOn
12 Burczynski, M.E. et al. Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells. Toxicol. Sci. 58, 399-415 (2000)   DOI
13 Xian, C.J., Cool, J.C., Howarth, G.S. & Read, L.C. Effects of TGF-alpha gene knockout on epithelial cell kinetics and repair of methotrexate-induced damage in mouse small intestine. J. Cell Physiol. 191, 105-115 (2002).   DOI   ScienceOn
14 Thai, S.F., Allen, J.W., DeAngelo, A.B. & George, M.H. Altered gene expression in mouse livers after dichloroacetic acid exposure. Mutat. Res. 543, 167-180 (2003)   DOI   ScienceOn
15 Wan, S.L. et al. The intelligent data management system for Toxicogenomics. J. Vet. Med. Sci. 66, 1334-1338 (2004)
16 Caetano, N.N., Campello, A.P., Carnieri, E.G., Kluppel, M.L. & Oliveira M.B. Effect of methotrexate (MTX) on NAD (P)+ dehydrogenases of HeLa cells: malic enzyme, 2-oxoglutarate and isocitrate dehydrogenases. Cell Biochem. Funct. 15, 259-264 (1997)   DOI   ScienceOn
17 Chauhan, S.S. et al. Reduced endocytosis and altered lysosome function in cisplatin-resistant cell lines. Br. J. Cancer. 88, 1327-1334 (2003)   DOI   ScienceOn
18 Affleck, J.G., Neumann, K., Wong, L. & Walker, V.K. The Effects of Methotrexate on Drosophila Development, Female Fecundity, and Gene Expression. Toxicol. Sci. Nov. 9 (2005)
19 Kroll, D.J., Borgert, C.J., Wiedmann, T.W. & Rowe T.C. Drug sensitivity of heat-resistant mouse B16 melanoma variants. Radiat Res. 124, 15-21 (1990)   DOI   ScienceOn
20 Notenboom, S. et al. Short-term exposure of renal proximal tubules to gentamicin increases long-term multidrug resistance protein 2 (abcc2) transport function and reduces nephrotoxicant sensitivity. J. Pharmacol Exp. Ther. 315, 912-920 (2005)
21 Machy, P., Arnold, B., Alino, S. & Leserman, L.D. Interferon sensitive and insensitive MHC variants of a murine thymoma differentially resistant to methotrexate- containing antibody-directed liposomes and immunotoxin. J. Immunol. 136, 3110-3115 (1986)