Gene Expression Profiling of Human Bronchial Epithelial (BEAS-2B) Cells Treated with Nitrofurantoin, a Pulmonary Toxicant

  • Kim, Youn-Jung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology) ;
  • Song, Mee (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology) ;
  • Ryu, Jae-Chun (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology)
  • Published : 2007.12.31

Abstract

Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.

Keywords

References

  1. Williams, E. M. & Triller, D. M. Recurrent acute nitrofurantoin- induced pulmonary toxicity. Pharmacotherapy 26:713-718 (2006) https://doi.org/10.1592/phco.26.5.713
  2. Bobbak, V. & Bernadette, M. M. Nitrofurantoin pulmonary toxicity: A brief review. Cur Respir Med Rev 2:439-442 (2006) https://doi.org/10.2174/157339806778777276
  3. Adamson, I. Y. Drug-induced pulmonary fibrosis. Environ Health Perspect 55:25-36 (1984) https://doi.org/10.2307/3429689
  4. Daba, M. H., El-Tahir, K. E., Al-Arifi, M. N. & Gubara, O. A. Drug-induced pulmonary fibrosis. Saudi Med 25:700-706 (2004)
  5. Gram, T. E. Chemically reactive intermediates and pulmonary xenobiotic toxicity. Pharmacol Rev 49: 297-341 (1997)
  6. Pourahmad, J., Khan, S. & O'Brien, P. J. Lysosomal oxidative stress cytotoxicity induced by nitrofurantoin redox cycling in hepatocytes. Adv Exp Med Biol 500:261-265 (2001)
  7. Ryu, J. C., Kim, M. K., Choi, M. H. & Chun, T. H. Promising next generation technology in toxicology-toxicogenomics. Mol Cell Toxicol 1:1-6 (2005)
  8. Ashburne, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25-29 (2000) https://doi.org/10.1038/75556
  9. Tatsuya, K. et al. Event Ontology: A Pathway-Centric Ontology for Biological Processes. Pac Symp Biocomput 11:152-163 (2006)
  10. Te Pas, M. F. et al. Biochemical pathways analysis of microarray results: regulation of myogenesis in pigs. BMC Dev Biol 7:66-80 (2007) https://doi.org/10.1186/1471-213X-7-66
  11. Mossman, B. T., Lounsbury, K. M. & Reddy, S. P. Oxidants and signaling by mitogen-activated protein kinases in lung epithelium. Am J Respir Cell Mol Biol 34:666-669 (2006) https://doi.org/10.1165/rcmb.2006-0047SF
  12. Park, H. J. et al. Identification of Gene-based potential biomarkers for cephalexin-induced nephrotoxicity in mice. Mol Cell Toxicol 2:193-201 (2006)
  13. Chen, C. M. et al. Up-regulation of connective tissue growth factor in hyperoxia-induced lung fibrosis. Pediatr Res 62:128-133 (2007) https://doi.org/10.1203/PDR.0b013e3180987202
  14. Wang, X. M. et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med 203:2895-2906 (2006) https://doi.org/10.1084/jem.20061536
  15. Fridlender, Z. G. et al. Telomerase activity in bleomycin- induced epithelial cell apoptosis and lung fibrosis. Eur Respir J 30:205-213 (2007) https://doi.org/10.1183/09031936.00009407
  16. Sheppard, M. N. & Thurlow, N. P. Distribution of the cytoskeletal protein beta-tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumors. Histopathology 20:421-425 (1992) https://doi.org/10.1111/j.1365-2559.1992.tb01013.x
  17. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63 (1983) https://doi.org/10.1016/0022-1759(83)90303-4
  18. Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121 (2001)