Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Gene Expression Analysis of the Bromobenzene Treated Liver with Non-hepatotoxic Doses in Mice

  • Lim, Jung-Sun (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Jeong, Sun-Young (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Hwang, Ji-Yoon (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Park, Han-Jin (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Cho, Jae-Woo (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Song, Chang-Woo (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Kim, Yang-Seok (Bioinformatics Division, ISTECH Inc.) ;
  • Lee, Wan-Seon (Bioinformatics Division, ISTECH Inc.) ;
  • Moon, Jin-Hee (Bioinformatics Division, ISTECH Inc.) ;
  • Han, Sang-Seop (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Yoon, Seok-Joo (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology)
  • Published : 2005.12.30
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Abstract

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

Keywords

References

  1. Stefan, U.R. et al. Genomics and proteomics analysis of acetaminophen toxicity in mouse liver. Toxicol. Sci. 65, 135-150 (2002) https://doi.org/10.1093/toxsci/65.1.135
  2. Fountoulakis, M. et al. Modulation of gene and protein expression by carbon tetrachloride in the rat liver. Toxicol. Appl. Pharmacol. 183, 71-80 (2002) https://doi.org/10.1006/taap.2002.9460
  3. Heijne, W.H., Stierum, R.H., Slijper, M, van Bladeren, P.J. & van Ommen, B. Toxicogenomics of bromobenzene hepatotoxicity: a combined transcriptomics and proteomics approach. Biochem. Pharmacol. 1, 857-875 (2003)
  4. Higgins, M.A. et al. Gene expression analysis of the acute phase response using a canine microarray. Toxicol. Sci. 74, 470-484 (2003) https://doi.org/10.1093/toxsci/kfg142
  5. Heijne, W.H. et al. Bromobenzene-induced hepatotoxicity at the transcriptome level. Toxicol. Sci. 79, 411-422 (2004) https://doi.org/10.1093/toxsci/kfh128
  6. Heijne, W.H., Jonker, D., Stierum, R.H., Ommen, B.V. & Groten, J.P. Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure. Mutat. Res. 575, 85-101 (2005) https://doi.org/10.1016/j.mrfmmm.2005.02.003
  7. Wang, H., Peng, R., Wu, D. & Li, S. Serum glutathione S-transferase in bromobenzene-induced acute Non-hepatotoxic Doses Treatment of Bromobenzene 273 hepato-toxicity in mice. Wei Sheng Yan Jiu. 30(3), 135-137 (2001).
  8. Wong, S.G., Card, J.W. & Racz, W.J. The role of mitochondrial injury in bromobenzene and furosemide induced hepatotoxicity. Toxicol. Lett. 116(3), 171-181 (2000) https://doi.org/10.1016/S0378-4274(00)00218-6
  9. Szymanska, J.A. Hepatotoxicity of brominated benzenes: relationship between chemical structure and hepatotoxic effects in acute intoxication of mice. Arch. Toxicol. 72(2), 97-103 (1998) https://doi.org/10.1007/s002040050474
  10. James, R., Desmond, P., Kupfer, A., Schenker, S. & Branch, R.A. The differential localization of various drug metabolizing systems within the rat liver lobule as determined by the hepatotoxins allyl alcohol, carbon tetrachloride and bromobenzene. J. Pharmacol. Exp. Ther. 217, 127-132 (1981)
  11. Den Besten, C., Brouwer, A., Rietjens, I.M. & van Bladeren, P.J. Biotransformation and toxicity of halogenated halogenated benzenes. Hum. Exp. Toxicol. 13(12), 866- 875 (1994) https://doi.org/10.1177/096032719401301209
  12. Lovern, M.R., Cole, C.E. & Schlosser, P.M. A review of quantitative studies of benzene metabolism. Crit. Rev. Toxicol. 31(3), 285-311 (2001) https://doi.org/10.1080/20014091111703
  13. Sabourin, P.J. et al. Effect of exposure concentration, exposure rate, and route of administration on metabolism of benzene by F344 rats and B6C3F1 mice. Toxicol. Appl. Pharmacol. 99, 421-444 (1989) https://doi.org/10.1016/0041-008X(89)90151-8
  14. Bartosiewicz, M.J. et al. Unique gene expression patterns in liver and kidney associated with exposure to chemical toxicants. J. Pharmacol. Exp. Ther. 297, 895-905 (2001)
  15. Koen, Y.M. & Hanzlik, R.P. Identification of seven proteins in the endoplasmic reticulum as targets for reactive metabolites of bromobenzene. Chem. Res. Toxicol. 15(5), 699-706 (2002) https://doi.org/10.1021/tx0101898