Lovastatin induces mitotic abnormalities in various cell lines.
We examined the effects of lovastatin, a common anti-atherosclerotic drug and a blocker of the cell cycle, on the process of mitosis. It is known that lovastatin induces an arrest or a retardation of the cell cycle in many cell types not only at the G(1)phase, but also at the G(2)/M transition. After 24-48 h incubation of epithelial PtK(2), T24, HeLa cells and fibroblastic L929 cells in the presence of 1. 0-60.0 microm lovastatin, diverse mitotic perturbations have been observed. The most noteworthy phenomena recorded were prometaphase retardation and chromosome lagging during metaphase and anaphase. After the recovery in lovastatin-free media, the cells continued mitosis without any disturbances. Mevalonic acid prevented the effects of lovastatin. We conclude that the effects were specific for lovastatin-induced inhibition of mevalonic acid synthesis. Immunofluorescence studies with anticentromeric antibodies suggested that one of the possible causes of the lovastatin-induced mitotic disorder could be an interference with the development and function of the centromeres.
Lamprecht
J
J
Department of Histology and Embryology, Medical University of Warsaw, Chalubińskiego 5, Warsaw, 02-004, Poland.
Wójcik
C
C
Jakóbisiak
M
M
Stoehr
M
M
Schrorter
D
D
Paweletz
N
N
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002460:Cell Line; D002503:Centromere / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*
D000924:Anticholesteremic Agents; D008148:Lovastatin; D008798:Mevalonic Acid