Induction of multinucleated cells in V79 Chinese hamster cells exposed to dimethylarsinic acid, a methylated derivative of inorganic arsenics: mechanism associated with the formation of aberrant mitotic spindles

Abstract

Induction of multinucleated cells in V79 Chinese hamster cells exposed to dimethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, and the mechanism of induction were investigated in terms of cytoskeletal changes. DMAA caused mitotic arrest and concomitant induction of multinucleated cells. Arsenite was less effective than DMAA in causing mitotic arrest and in inducing multinucleated cells. Analysis by videograph and a study of post-mitotic incubation of cells arrested in metaphase by DMAA demonstrated that the cells escaped from metaphase with ameboid behaviour and pseudopodia, but they did not divide into daughter cells, thereby resulting in multinucleated cells. During the post-mitotic incubation in the presence of DMAA, the cells did not proliferate but retained their capacity to synthesize DNA. DMAA caused disappearance of the microtubule network in interphase cells, but did not influence the organization of actin stress fibres. Furthermore, DMAA caused aberrations of mitotic microtubules, such as tripolar or quadripolar spindles and aster-like spindles, in a concentration-dependent manner. These results suggest that DMAA specifically acted on the microtubules and that multinucleated cells appeared when cells with aberrant spindles escaped from metaphase to advance the cell cycle and the nuclear membranes were regenerated.