Abstract
The concentration dependent effects of griseofulvin (GF) on mitosis in PtK1 cells were studied using a combination of time lapse cinematography and polarization and electron microscopy. Low concentrations of GF (4×10−5 M) allowed a substantial number of cells to enter and complete an apparently normal mitosis. At higher concentrations of GF (1×10−4 M and 2.5×10−4 M) all cells entering mitosis were arrested. Typical c-mitotic chromosome arrays were observed at 1×10−4 M GF with microtubules present but no spindle formed. At 2.5×10−4 M GF chromosomes did not orient toward a common center to form a c-mitotic figure, but instead remained in a loosely clustered grouping at the center of the cell. Electron microscopy showed microtubules to be absent but revealed an irregularly shaped electron dense cloud around the centrioles. Quantitative polarization microscopy of metaphase cells perfused with GF showed rapid loss of spindle birefringence after exposure to the drug. Coinciding with loss of birefringence the spindle shrank rapidly with a pronounced shortening of pole to pole distance.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brinkley, B.R., Stubblefield, E., Hsu, T.C.: Effects of colcemid inhibition of CHO cells in vitro. J. Ultrastruct. Res. 19, 1–18 (1967)
Deysson, G.: Sur les properietés antimitotiques de la griseofulvine. Ann. Pharm. françaises 22, 17–25 (1964)
Grisham, L., Wilson, L., Bensch, K.: Antimitotic action of griseofulvin does not involve disruption of microtubules. Nature (Lond.) 244, 294–296 (1973)
Gull, K., Trinci, A.P.J.: Griseofulvin inhibits fungal mitosis. Nature (Lond.) 244, 292–294 (1973)
Malawista, S.E., Sato, H., Bensch, K.G.: Vinblastine and griseofulvin reversibly disrupt the living mitotic spindle. Science 160, 770–771 (1968)
Malawista, S.E., Sato, H., Creasey, A.: Dissociation of the mitotic spindle in oocytes exposed to griseofulvin and vinblastine. Exp. Cell Res. 99, 193–197 (1976)
Margolis, R.L., Wilson, L.: Addition of colchicine-tubulin complex to microtubule ends: The mechanism of substoichiometric colchicine poisioning. Proc. nat. Acad. Sci. (Wash.) 74, 3466–3470 (1977)
Mullins, J.M., Biesele, J.J.: Terminal phase of cytokinesis in D-98S cells. J. Cell Biol. 73, 672–684 (1977)
Murphy, D.B., Johnson, K.A., Borisy, G.G.: The mechanism of the stimulation of tubulin assembly by high molecular weight proteins. J. Cell Biol. 70, 225a (1976)
Paget, E.G., Walpole, A.: Some cytological effects of griseofulvin. Nature (Lond.) 182, 1320–1321 (1958)
Robbins, E., Jentzsch, G., Micali, A.: The centriole cycle in synchronized HeLa cells. J. Cell Biol. 36, 329–339 (1968)
Roobol, A., Gull, K., Pogson, I.: Inhibition by griseofulvin of microtubule assembly in vitro. FEBS Letters 67, 248–251 (1976)
Roos, U-P.: Light and electron microscopy of rat kangaroos cells in mitosis. II. Kinetochore structure and function. Chromosoma (Berl.) 41, 195–220
Sato, H., Ellis, G., Inoué, S.: Microtubular origin of mitotic spindle form birefringence. J. Cell Biol. 67, 501–517 (1975)
Sloboda, R.D., Malawista, S., Blaricom, G. Van, Creasey, W., Rosenbaum, J.: Griseofulvin: association with tubulin and inhibition of in vitro microtubule assembly. J. Cell Biol. 70, 290a (1976)
Snyder, J.A., McIntosh, J.R.: Initiation and growth of microtubules from mitotic centers in lysed mammalian cells. J. Cell Biol. 67, 744–760
Weber, K., Wehland, J., Herzog, W.: Griseofulvin interacts with microtubules both in vivo and in vitro. J. molec. Biol. 102, 817–829 (1976)
Wilson, L., Bryan, J.: Biochemical and pharmacological properties of microtubules. In: Advanc. Cell molec. Biol., Vol. 3 pp 21–72. New York: Academic Press, Inc. 1974
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mullins, J.M., Snyder, J.A. Effects of griseofulvin on mitosis in PtK1 cells. Chromosoma 72, 105–113 (1979). https://doi.org/10.1007/BF00286432
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00286432