Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells.
Arsenical compounds, known to be human carcinogens, were shown to disturb cell cycle progression and induce cytogenetic alterations in a variety of cell systems. We report here that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35% of the total cell population was arrested at the mitotic stage after treatment with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells. Under a microscope, we observed abnormal mitotic figures in arsenite-arrested mitotic cells, including deranged chromosome congression, elongated polar distance of mitotic spindle, and enhanced microtubule immunofluorescence. The spindle microtubules of arsenite-arrested mitotic cells were more resistant to nocodazole-induced dissolution than those of control mitotic cells. According to turbidity assay, arsenite at concentrations below 100 microM significantly enhanced polymerization of tubulins. Since spindle dynamics play a crucial role in mitotic progression, our results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.
Huang
S C
SC
Institute of Biomedical Sciences, Academia Sinica, National Defense Medical Center, Taipei, Taiwan, ROC.
Lee
T C
TC
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002877:Chromosomes, Human; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects*
D018053:Arsenites; D018797:Cell Cycle Proteins; D008868:Microtubule Proteins; C015001:arsenite