Subcutaneous Four-Week Repeated Dose Toxicity Studies of Rice Cell-Derived Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor in Rats
Tóm tắt
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 µg/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.
Tài liệu tham khảo
Armitage, J.O. (1998). Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood, 92, 4491–4508.
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.
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.
Doran, P. (2000). Foreign protein production in plant tissue cultures. Trends Biotechnol., 11, 199–204.
Dorr, R.T. (1993). Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte-macrophage colonystimulating factor. Clin. Ther., 15, 19–29.
Giddings, G. (2001). Transgenic plants as protein factories. Curr. Opin. Biotechnol., 12, 450–454.
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.
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.
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.
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.
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.
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.
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.
Lieschke, G.J. and Burgess, A.W. (1992). Granulocyte colonystimulating factor and granulocyte-macrophage colonystimulating factor. N. Engl. J. Med., 327, 99–106.
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.
Metcalf, D. (1991). Control of granulocytes and macropharges: molecular, cellular, and clinical aspects. Science, 254, 529–533.
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.
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.
Rasko, J.E. and Gough, N.M. (1994). Granulocyte-macrophage colony stimulating factor: The cytokine handbook (Thomson, Ed.). Academic Press, London, pp. 343–369.
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.
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.
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.
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.
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.
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.
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.
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.