Browse > Article
http://dx.doi.org/10.5487/TR.2008.24.4.315

Subcutaneous Four-Week Repeated Dose Toxicity Studies of Rice Cell-Derived Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor in Rats  

Ji, Jung-Eun (Department of Environmental & Health Chemistry)
Lee, Jung-Min (Department of Environmental & Health Chemistry)
Choi, Jong-Min (Department of Environmental & Health Chemistry)
Choi, Young-Hwa (Department of Environmental & Health Chemistry)
Kim, Eun-Kyung (Department of Environmental & Health Chemistry)
Chu, So-Jung (Department of Environmental & Health Chemistry)
Kim, Seok-Kyun (Department of Environmental & Health Chemistry)
Ahn, Kyong-Hoon (Department of Environmental & Health Chemistry)
Lee, Dong-Hoon (Department of Environmental & Health Chemistry)
Kim, Ha-Hyung (Physical Pharmacy Laboratory, College of Pharmacy, Chung-Ang University)
Han, Kyu-Boem (Hanson Biotech Co., Ltd)
Kim, Dae-Kyong (Department of Environmental & Health Chemistry)
Publication Information
Toxicological Research / v.24, no.4, 2008 , pp. 315-320 More about this Journal
Abstract
Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) is a glycoprotein and hematopoietic growth factors that regulates the proliferation of myeloid precursor cells and activates mature granulocytes and macrophages. In a previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study, we examined the repeated dose toxicity of rhGM-CSF in SD rats. The repeated dose toxicity study was performed at each dose of 50 and 200 ${\mu}g/kg$ subcutaneous administration of rhGM-CSF everyday for 28-days period. The results did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the tested groups. The hematological and blood biochemical parameters were statistically not different in all groups. These results suggest that rhGM-CSF may show no repeated dose toxicity in SD rats under the conditions.
Keywords
Recombinant hGM-CSF; Rice cells; Repeated dose toxicity; SD rats;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Armitage, J.O. (1998). Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood, 92, 4491-4508
2 Kim, H.J., Lee, D.H., Kim, D.K., Han G.B. and Kim, H.J. (2008). The glycosylation and in vivo stability of human granulocyte-macrophage colony-stimulating factor produced in rice cells. Biol. Pharm. Bull., 31, 290-294   DOI   ScienceOn
3 Song, Z.P., Lu, B.R., Zhu, Y.G. and Chen, J.K. (2003). Gene flow from cultivated rice to the wild species Oryza rufipogon under experimental field conditions. New Phytol., 157, 657-665   DOI   ScienceOn
4 Vazquez, J.A., Gupta, S. and Villanueva, A. (1998). Potential utility of recombinant human GM-CSF as adjunctive treatment of refractory oropharyngeal candidiasis in AIDS patients. Eur. J. Clin. Microbiol. Infect. Dis., 17, 781-783   DOI
5 Metcalf, D. (1991). Control of granulocytes and macropharges: molecular, cellular, and clinical aspects. Science, 254, 529- 533   DOI
6 Okamoto, M., Nakai, M., Nakayama, C., Yanagi, H., Matsui, H., Noguchi, H., Namiki, M., Sakai, J., Kadota, K. and Fukui, M. (1991). Purification and characterization of three forms of differently glycosylated recombinant human granulocyte- macrophage colony-stimulating factor. Arch. Biochem. Biophys., 286, 562-568   DOI   ScienceOn
7 Doran, P. (2000). Foreign protein production in plant tissue cultures. Trends Biotechnol., 11, 199-204
8 Vandekerckhove, J., Damme, J., van Lijsebettens, M., Botterman, J., De Block, M., Vandewiele, M., De Clercq, A., Leemans, J., van Montagu, M. and Krebbers, E. (1989). Enkephalins produced in transgenic plants using modified 2S seed storage proteins. Biotechnology (N.Y.), 7, 929-932   DOI
9 Shin, Y.J., Hong, S.Y., Kwon, T.H., Jang, Y.S. and Yang, M.S. (2003). High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture. Biotechnol. Bioeng., 82, 778-783   DOI   ScienceOn
10 Lee, F., Yokota, T., Otsuka, T., Gemmell, L., Larson, N., Luh, J., Aria, K. and Rennick, D. (1985). Isolation of cDNA for a human granulocyte-macropharge colony-stimulating factor by functional expression in mammalian cells. Proc.Natl. Acad. Sci. USA, 82, 4360-4364   DOI
11 Cho, S.A., Park, J.H., Seok, S.H., Juhn, J.H., Kim, S.J., Ji, H.J., Choo, Y.S. and Park, J.H. (2006). Effect of granulocyte macrophage-colony stimulating factor (GM-CSF) on 5- FU-induced ulcerative mucositis in hamster buccal pouches. Exper. Toxicol. Pathol., 57, 321-328   DOI   ScienceOn
12 Kim, Y.C., Kim, H.J., Kong, M.K., Lim, A.K., Kwon, M.H., Kim, K.S. and Lee, G.D. (2007). Single and four-week repeated oral toxicity study of antidiabetic herb extract microcapsule in sprague-dawley rats. J. Toxicol. Pub. Health, 23, 87-96   과학기술학회마을   DOI   ScienceOn
13 Krumwieh, D., Weinmann, E., Siebold, B. and Seiler, FR. (1990). Preclinical studies on synergistic effects of IL-1, IL-3, G-CSF and GM-CSF in cynomolgus monkeys. Int. J. Cell Cloning, 8, 229-248   DOI
14 Ragnhammar, P., Friesen, H.J., Frodin, J.E., Lefvert, A.K., Hassan, M., Osterborg, A. and Mellstedt, H. (1994). Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients. Blood, 84, 4078-4087
15 Sardana, R., Dudani, A.K., Tackaberry, E., Alli, Z., Porter, S., Rowlandson, K., Ganz, P. and Altosaar, I. (2007). Biologically active human GM-CSF produced in seeds of transgenic rice plants. Transgenic Res., 16, 713-721   DOI
16 Lowry, N.J., Rosebrough, A.L., Farr, R.J. and Randall. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265-275
17 Lieschke, G.J. and Burgess, A.W. (1992). Granulocyte colonystimulating factor and granulocyte-macrophage colonystimulating factor. N. Engl. J. Med., 327, 99-106   DOI   ScienceOn
18 Wong, G.G., Witek, J.S., Temple, P.A., Wikens, K.M., Leary, A.C., Luxenberg, D.P., Jones, S.S., Brown, E.L., Kay, R.M., Orr, E.C., Shoemaker, C., Golde, D.W., Kaufman, R.J., Hewick, R.M., Wang, E.A. and Clark, S.C. (1985). Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science, 228, 810-815   DOI
19 Cantrell, M.A., Anderson, D., Cerretti, D.P., Price, V., Mckereghan, K., Tushinski, R.J., Mochizuki, D.Y., Larsen, A., Grabstein, K., Gillis, S. and Cosman, D. (1985). Cloning, sequencing, and expression of a human granulocyte/macropharge colony-stimulating factor. Proc. Natl. Acad. Sci. USA, 82, 6250-6254   DOI
20 Song, S.W., Jung, W. and Hong, D.H. (2006). Thirteen-week repeated-dose toxicity studies of STB-HO-BM in rats. J. Toxicol. Pub. Health, 22, 135-144   과학기술학회마을
21 Ji, J.E., Lee, J.M., Choi, J.M., Choi, Y.H., Kim, S.K., Ahn, K.H., Lee, D.H., Kim, H.H., Han, K.B. and Kim, D.K. (2007). Intravenous single and two week repeated dose toxicity studies of rice cells-derived recombinant human granulocyte-macrophage colony-stimulating factor on rats. J. Toxicol. Pub. Health, 23, 383-389   과학기술학회마을   DOI   ScienceOn
22 Dorr, R.T. (1993). Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte-macrophage colony stimulating factor. Clin. Ther., 15, 19-29
23 Han, J.H., Hesson Chung, Lee, J.H., Suh, J.E., Lee, G.S., Kim, J.C. and Kang, B.H. (2004). Single and two-week repeated oral dose toxicity study of DHP2, a hydrophobic drug delivery vehicle in mice. J. Toxicol. Pub. Health, 20, 123-129
24 Giddings, G. (2001). Transgenic plants as protein factories. Curr. Opin. Biotechnol., 12, 450-454   DOI   ScienceOn
25 Wadhwa, M., Skog, A.-L., Bird, C., Ragnhammar, P., Liljefors, M., Gaines-Das, R., Mellstedt, H. and Thorpe, R. (1999). Immunogenicity of granulocyte-macrophage colonystimulating factor (GM-CSF) products in patients undergoing combination therapy with GM-CSF. Clin. Cancer Res., 5, 1353-1361
26 Hovgaard, D., Mortensen, B.T., Schifter, S. and Nissen, N.I. (1993). Comparative pharmacokinetics of single-dose administration of mammalian and bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor. Eur. J. Haematol., 50, 32-36
27 Rasko, J.E. and Gough, N.M. (1994). Granulocyte-macrophage colony stimulating factor: The cytokine handbook (Thomson, Ed.). Academic Press, London, pp. 343-369