Effects of griseofulvin on mitosis in PtK1 cells.

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 X 10(-5) M) allowed a substantial number of cells to enter and complete an apparently normal mitosis. At higher concentrations of GF (1 X 10(-4) M and 2.5 X 10(-4) M) all cells entering mitosis were arrested. Typical c-mitotic chromosome arrays were observed at 1 X 10(-4) M GF with microtubules present but no spindle formed. At 2.5 X 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 microtubles to be absent but revealed in 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.