Hostname: page-component-848d4c4894-mwx4w Total loading time: 0 Render date: 2024-06-25T15:47:26.146Z Has data issue: false hasContentIssue false

The effect of drugs on the cell cycle of Giardia intestinalis

Published online by Cambridge University Press:  06 April 2009

G. F. Hoyne
Affiliation:
Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006
P. F.L. Boreham
Affiliation:
Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006
P. G. Parsons
Affiliation:
Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006
C. Ward
Affiliation:
Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006
B. Biggs
Affiliation:
Queensland Institute of Medical Research, Bramston Terrace, Herston, Brisbane, Queensland, Australia 4006

Summary

Flow cytometric analysis of the binucleated protozoan parasite Giardia intestinalis gave DNA histograms with a broad Gl peak and a definable G2 + M peak with twice the DNA content of Gl. Twenty-four hour treatment with metronidazole arrested cell cycle progression of susceptible trophozoites in the G2 + M phase, but had no effect, even at toxic doses, on the DNA histogram of a line selected for resistance to metronidazole. Furazolidone was inhibitory to both stocks, causing an arrest in the S and G2 + M phases. Inhibitors of the mammalian cell cycle were also tested. Hydroxyurea, which blocks mammalian cells in Gl/S, and razoxane, which blocks in G2 + M, arrested trophozoites in the G2 + M phase whereas colchicine and gamma-irradiation had little or no effect on the cell cycle of G. intestinalis. These results suggest that the cell cycle of G. intestinalis may be controlled in a different manner from mammalian cells.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adam, R. D., Nash, T. E. & Wellems, T. E. (1988). The Giardia lamblia trophozoite contains sets of closely related chromosomes. Nucleic Acids Research 16, 4555–67.CrossRefGoogle ScholarPubMed
Boreham, P. F. L. (1987). Transmission of Giardia by food and water. Food Technology in Australia 39, 61–3.Google Scholar
Boreham, P. F. L., Phillips, R. E. & Shepherd, R. W. (1984). The sensitivity of Giardia intestinalis to drugs in vitro. Journal of Antimicrobial Chemotherapy 14, 449–61.CrossRefGoogle ScholarPubMed
Boreham, P. F. L., Phillips, R. E. & Shepherd, R. W. (1985). A comparison of in vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis. Journal of Antimicrobial Chemotherapy 16, 589–95.CrossRefGoogle ScholarPubMed
Boreham, P. F. L., Phillips, R. E. & Shepherd, R. W. (1988). Altered uptake of metronidazole in vitro by stocks of Giardia intestinalis with different drug sensitivities. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 104–6.CrossRefGoogle ScholarPubMed
Boreham, p. F. L. & Shepherd, R. W. (1984). Giardiasis in child-care centres. Medical Journal of Australia 2, 263.CrossRefGoogle Scholar
Davidson, R. A. (1984). Issues in clinical parasitology: the treatment of giardiasis. American Journal of Gastroenterology 79, 256–61.Google ScholarPubMed
Franklin, R. M., Brun, R. & Grieder, A. (1986). Microscopic and flow cytophotometric analysis of parasitemia in cultures of Plasmodium falciparum vitally stained with Hoechst 33342 - application to study of antimalarial agents. Zeitschrift für Parasitenkunde 72, 201–12.CrossRefGoogle ScholarPubMed
Glick, B. (1985). Flow cytometric analysis of the cell cycle with reference to B-cells. Diagnostic Immunology 3, 5761.Google ScholarPubMed
Gray, J. W. (1976). Cell cycle analysis of perturbed cell populations: computer simulation of sequential DNA distributions. Cell and Tissue Kinetics 9, 499516.Google ScholarPubMed
Gray, J. W., Dean, P. N. & Mendelsohn, M. L. (1979). Quantitative cell-cycle analysis. In Flow Cytometry and Sorting (ed. Melamed, M. R., Mullaney, P. F. & Mendelsohn, J. L.) New York: John Wiley and Sons Inc. pp. 383408.Google Scholar
Hare, J. D. & Bahler, D. W. (1986). Analysis of Plasmodium falciparum growth in culture using Acridine Orange and flow cytometry. Journal of Histochemistry and Cytochemistry 34, 215–20.CrossRefGoogle ScholarPubMed
Howard, A. & Pelc, S. R. (1986). Synthesis of deoxyribonucleic acid in normal and irradiated cells and its relation to chromosome breakage. International Journal of Radiation Biology 49, 207–18.Google Scholar
Iversen, O. H., Harket, G. & Rabe, R. (1986). Effects of hydroxyurea on the mitotic activity and the G2 phase in hairless mouse epidermis. Cell and Tissue Kinetics 19, 257–65.Google ScholarPubMed
Janse, C. J., Van Vianen, P. H., Tanke, H. J., Mons, B., Ponnudurai, T. & Overdulve, J. P. (1987). Plasmodium species: flow cytometry and microfluorometry assessment of DNA content and synthesis. Experimental Parasitology 64, 8894.CrossRefGoogle ScholarPubMed
Keister, D. B. (1983). Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. Transactions of the Royal Society of Tropical Medicine and Hygiene 77, 487–8.CrossRefGoogle ScholarPubMed
Kinosian, B., Gilman, R. H., Ordonez, J., O'Hare, J., Wahl, S., Koster, F. & Spira, W. (1988). Cell injury in Giardia lamblia detected by forward light scatter. In Advances in Giardia Research (ed. Wallis, P. M. & Hammond, B. R.), Calgary: The University of Calgary Press. pp. 913.Google Scholar
Mcintyre, P., Boreham, P. F. L., Phillips, R. E. & Shepherd, R. w. (1986). Chemotherapy in Giardiasis: clinical response and in vitro drug sensitivity of human isolates in axenic culture. Journal of Pediatrics 108, 1005–10.CrossRefGoogle ScholarPubMed
Muller, M. (1983). Mode of action of metronidazole on anaerobic bacteria and protozoa. Surgery 93, 165–71.Google ScholarPubMed
Phillips, R. E., Boreham, P. F. L. & Shepherd, R. W. (1984). Cryopreservation of viable Giardia intestinalis trophozoites. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 604–6.CrossRefGoogle ScholarPubMed
Rao, P. N. (1980). The molecular basis of drug-induced G2 arrest in mammalian cells. Molecular and Cellular Biochemistry 29, 4757.CrossRefGoogle ScholarPubMed
Rizzoni, M. & Palitti, F. (1973). Regulatory mechanism of cell division. I. Colchicine-induced endoreduplication. Experimental Cell Research 77, 450–8.CrossRefGoogle ScholarPubMed
Ronot, X., Hecquet, C., Larno, S., Hainque, B. & Aldophe, M. (1986). G2 arrest, binucleation and single parameter DNA flow cytometric analysis. Cytometry 7, 286–90.CrossRefGoogle ScholarPubMed
Saul, A., Myler, P., Mangan, T. & Kidson, C. (1982). Plasmodium falciparum: automated assay of erythrocyte invasion using flow cytometry. Experimental Parasitology 54, 6471.CrossRefGoogle Scholar
Smith, N. C., Bryant, C. & Boreham, P. F. L. (1988). Possible roles for pyruvate: ferredoxin oxidoreductase and thiol-dependent peroxidase and reductase activities in resistance to nitroheterocyclic drugs in Giardia intestinalis. International Journal for Parasitology 18, 991–7.CrossRefGoogle ScholarPubMed
Sutherland, R. L., Hall, R. E. & Taylor, I. W. (1983). Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Research 43, 39984006.Google ScholarPubMed
Taylor, I. w. & Bleehen, N. M. (1978). Razoxaneinduced polyploidy. British Journal of Cancer 38, 143–7.CrossRefGoogle ScholarPubMed
Taylor, I. w. & Milthorpe, B. K. (1980). An evaluation of DNA fluorochromes, staining techniques, and analysis for flow cytometry. I. Unperturbed cell populations. Journal of Histochemistry and Cytochemistry 28, 1124–32.CrossRefGoogle ScholarPubMed
Upcroft, J. A., Boreham, P. F. L. & Upcroft, P. (1989). Geographic variation of Giardia karyotypes. International Journal for Parasitology (in the Press).CrossRefGoogle ScholarPubMed
Wiesenhahn, G. P., Jarrol, E. L., Lindmark, D. G., Meyer, E. A. & Hallick, L. M. (1984). Giardia lamblia: autoradiographic analysis of nuclear replicationa. Experimental Parasitology 58, 94100.CrossRefGoogle Scholar
Wolfe, M. s. (1979). Giardiasis. Pediatric Clinics of North America 26, 295303.CrossRefGoogle ScholarPubMed