Induction of centrosome injury, multipolar spindles and multipolar division in cultured V79 cells exposed to dimethylarsinic acid: role for microtubules in centrosome dynamics.
Role for microtubules in the induction of multiple microtubule organizing centers (MTOCs) and multipolar spindles by dimethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, was investigated with respect to the effects of microtubule disruption and reorganization. DMAA induced multiple signals of gamma-tubulin, a well-characterized component of MTOCs in the centrosome, in a manner specific to mitotic cells. The multiple signals of gamma-tubulin were co-localized with multipolar spindles caused by DMAA. Disruption of microtubules by nocodazole (NOZ) suppressed the appearance of centrosome injury caused by DMAA while disorganization of actin microfilaments by cytochalasin D did not. Post-treatment incubation of cells in which multiple signals of gamma-tubulin caused by DMAA had been coalesced to one or two dots by NOZ caused the reappearance of mitotic cells with multiple signals of gamma-tubulin, in conjunction with reorganization of the microtubules. These results suggest a role for microtubules in the dynamic behavior of the mitotic centrosome. DMAA induced aberrant cytokinesis, such as tripolar and quadripolar division, in a concentration-dependent manner. These results, together with the findings of earlier studies, suggest that the centrosome is the primary target for the induction of multipolar spindles by DMAA and the resultant induction of multinucleation and multipolar division.
Ochi
T
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Department of Toxicology and Environmental Health, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, 199-0195, Kanagawa, Japan. tkfmochi@pharm.teikyo-u.ac.jp
D000782:Aneuploidy; D000818:Animals; D002101:Cacodylic Acid / Q000633:toxicity*; D002453:Cell Cycle; D016923:Cell Death; D002478:Cells, Cultured; D018385:Centrosome / Q000187:drug effects*; D006224:Cricetinae; D008870:Microtubules / Q000502:physiology*; D008941:Spindle Apparatus / Q000187:drug effects*
D002101:Cacodylic Acid