S-adenosyl-L-methionine counteracts mitotic disturbances and cytostatic effects induced by sodium arsenite in HeLa cells.
Aneuploidy represents a serious problem for human health. Toxicological data have shown that aneuploidy can be caused by exposure to chemical agents known as mitotic spindle poisons, since they arrest cell cycle in mitosis through their interaction with tubulin. Among these agents is arsenic. In previous reports, we demonstrated that the aneugenic events induced by sodium arsenite can be abolished by the exogenous addition of S-adenosyl-l-methionine (SAM). Nevertheless, the mechanisms involved are still unknown. The aim of the present work was to study the influence of SAM on the mitotic disturbances caused by sodium arsenite. To achieve this goal, we analyzed microtubule (MT) polymerization by immunolocalization and live cell microscopy of mitotic cells. Our findings indicate that sodium arsenite alters the dynamics of MT polymerization, induces centrosome amplification and delays mitosis. Furthermore, SAM reduces the alterations on MT dynamics, as well as centrosome amplification, and therefore diminishes the formation of multipolar spindles in treated HeLa cells. In addition, SAM decreases the progression time through mitosis. Taking these data together, we consider that the mechanism by which SAM reduces the frequency of aneuploid cells must be related to the modulation of the dynamics and organization of MT, suggesting a role of SAM on chromosome segregation, which should be further investigated in primary cells.
Ramírez
Tzutzuy
T
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Stopper
Helga
H
Fischer
Thomas
T
Hock
Robert
R
Herrera
Luis A
LA
D018053:Arsenites / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects; D054697:Cytostatic Agents / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017670:Sodium Compounds / Q000037:antagonists & inhibitors*; D008941:Spindle Apparatus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D018053:Arsenites; D054697:Cytostatic Agents; D017670:Sodium Compounds; C017947:sodium arsenite; D012436:S-Adenosylmethionine