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http://dx.doi.org/10.4062/biomolther.2007.15.4.252

Comparing In Vitro and In Vivo Genomic Profiles Specific to Liver Toxicity Induced by Thioacetamide  

Kang, Jin-Seok (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Jeong, Youn-Kyoung (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Shin, Ji-He (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Suh, Soo-Kyung (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim, Joo-Hwan (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Lee, Eun-Mi (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim, Seung-Hee (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Park, Sue-Nie (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Publication Information
Biomolecules & Therapeutics / v.15, no.4, 2007 , pp. 252-260 More about this Journal
Abstract
As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.
Keywords
thioacetamide; in vivo; in vitro; toxicogenomics; hepatotoxicity; microarray;
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1 Waring, J. F., Jolly, R. A., Ciurlionis, R., Lum, P. Y., Praestgaard, J. T., Morfitt, D. C., Buratto, B., Roberts, C., Schadt, E. and Ulrich, R. G. (2001b). Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. Toxicol. Appl. Pharmacol. 175, 28-42   DOI   ScienceOn
2 Boverhof, D. R. and Zacharewski, T. R. (2006). Toxicogenomics in risk assessment: applications and needs. Toxicol. Sci. 89, 352-360   DOI   ScienceOn
3 Minami, K., Saito, T., Narahara, M., Tomita, H., Kato, H., Sugiyama, H., Katoh, M., Nakajima, M. and Yokoi, T. (2005). Relationship between hepatic gene expression profiles and hepatotoxicity in five typical hepatotoxicant-administered rats. Toxicol. Sci. 87, 296-305   DOI   ScienceOn
4 Bulera, S. J., Eddy, S. M., Ferguson, E., Jatkoe, T. A., Reindel, J. F., Bleavins, M. R. and De La Iglesia, F. A. (2001). RNA expression in the early characterization of hepatotoxicants in Wistar rats by high-density DNA microarrays. Hepatology 33, 1239-1258   DOI   ScienceOn
5 Corvi, R., Ahr, H. J., Albertini, S., Blakey, D. H., Clerici, L., Coecke, S., Douglas, G. R., Gribaldo, L., Groten, J. P., Haase, B., Hamernik, K., Hartung, T., Inoue, T., Indans, I., Maurici, D., Orphanides, G., Rembges, D., Sansone, S. A., Snape, J. R., Toda, E., Tong, W., van Delft, J. H., Weis, B. and Schechtman, L. M. (2006). Meeting report: Validation of toxicogenomicsbased test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use. Environ. Health Perspect. 114, 420- 429   DOI   ScienceOn
6 Dix, D. J., Houck, K. A., Martin, M. T., Richard, A. M., Setzer, R. W. and Kavlock, R. J. (2007). The ToxCast program for prioritizing toxicity testing of environmental chemicals. Toxicol. Sci. 95, 5-12   DOI   ScienceOn
7 Ellinger-Ziegelbauer, H., Stuart, B., Wahle, B., Bomann, W. and Ahr, H. J. (2004). Characteristic expression profiles induced by genotoxic carcinogens in rat liver. Toxicol. Sci. 77, 19-34   DOI   ScienceOn
8 Huang, Q., Jin, X., Gaillard, E. T., Knight, B. L., Pack, F. D., Stoltz, J. H., Jayadev, S. and Blanchard, K. T. (2004). Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. Mutat. Res. 549, 147-168   DOI   ScienceOn
9 James, L. P., Mayeux, P. R. and Hinson, J. A. (2003). Acetaminophen- induced hepatotoxicity. Drug. Metab. Dispos. 31, 1499-1506   DOI   ScienceOn
10 Hunter, A. L., Holscher, M. A. and Neal, R. A. (1977). Thioacetamide- induced hepatic necrosis. I. Involvement of the mixedfunction oxidase enzyme system. J. Pharmacol. Exp. Ther. 200, 439-448
11 Kang, J. S., Morimura, K., Salim, E. I., Wanibuchi, H., Yamaguchi, S. and Fukushima, S. (2005). Persistence of liver cirrhosis in association with proliferation of nonparenchymal cells and altered location of alpha-smooth muscle actin-positive cells. Toxicol. Pathol. 33, 329-335   DOI   ScienceOn
12 Kang, J.S., Wanibuchi, H., Wongpoomchai, R., Chusiri, Y., Gonzalez, F. J., Fukushima, S. (2007). Role of CYP2E1 in hepatotoxicity induced by thioacetamide. Toxicol. Appl. Pharmacol. In Press
13 Leighton, J. K., Brown, P., Ellis, A., Harlow, P., Harrouk, W., Pine, P. S., Robison, T., Rosario, L. and Thompson, K. (2006). Workgroup report: Review of genomics data based on experience with mock submissions--view of the CDER Pharmacology Toxicology Nonclinical Pharmacogenomics Subcommittee. Environ. Health Perspect. 114, 573-578   DOI   ScienceOn
14 Li, X., Benjamin, I. S. and Alexander, B. (2002). Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality. J. Hepatol. 36, 488-493   DOI   ScienceOn
15 Michel, C., Desdouets, C., Sacre-Salem, B., Gautier, J. C., Roberts, R. and Boitier, E. (2003). Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver. Am. J. Pathol. 163, 2191-2199   DOI   ScienceOn
16 Perkins, E. J., Bao, W., Guan, X., Ang, C. Y., Wolfinger, R. D., Chu, T. M., Meyer, S. A. and Inouye, L. S. (2006). Comparison of transcriptional responses in liver tissue and primary hepatocyte cell cultures after exposure to hexahydro-1, 3, 5- trinitro-1, 3, 5-triazine. BMC Bioinformatics 7 Suppl 4, S22
17 Muller, A., Machnik, F., Zimmermann, T. and Schubert, H. (1988). Thioacetamide-induced cirrhosis-like liver lesions in rats--usefulness and reliability of this animal model. Exp. Pathol. 34, 229-236   DOI   ScienceOn
18 Nieto, N., Friedman, S. L., Greenwel, P. and Cederbaum, A. I. (1999). CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells. Hepatology 30, 987-996   DOI
19 Pennie, W., Pettit, S. D. and Lord, P. G. (2004). Toxicogenomics in risk assessment: an overview of an HESI collaborative research program. Environ. Health Perspect. 112, 417-419
20 Porter, W. R., Gudzinowicz, M. J. and Neal, R. A. (1979). Thioacetamide- induced hepatic necrosis. II. Pharmacokinetics of thioacetamide and thioacetamide-S-oxide in the rat. J. Pharmacol. Exp. Ther. 208, 386-391
21 Ramaiah, S. K., Apte, U. and Mehendale, H. M. (2001). Cytochrome P4502E1 induction increases thioacetamide liver injury in diet-restricted rats. Drug Metab. Dispos. 29, 1088-1095
22 Wang, T., Shankar, K., Ronis, M. J. and Mehendale, H. M. (2000). Potentiation of thioacetamide liver injury in diabetic rats is due to induced CYP2E1. J. Pharmacol. Exp. Ther. 294, 473-479
23 Wang, X., Lu, Y. and Cederbaum, A. I. (2005). Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice. Hepatology 42, 400-410   DOI   ScienceOn
24 Zaragoza, A., Andres, D., Sarrion, D. and Cascales, M. (2000). Potentiation of thioacetamide hepatotoxicity by phenobarbital pretreatment in rats. Inducibility of FAD monooxygenase system and age effect. Chem. Biol. Interact. 124, 87-101   DOI   ScienceOn
25 Waring, J. F., Ciurlionis, R., Jolly, R. A., Heindel, M. and Ulrich, R. G. (2001a). Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity. Toxicol. Lett. 120, 359-368   DOI   ScienceOn
26 Waters, M. D. and Fostel, J. M. (2004). Toxicogenomics and systems toxicology: aims and prospects. Nat. Rev. Genet. 5, 936- 948   DOI   ScienceOn