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

Induction of multinucleated cells in V79 Chinese hamster cells exposed to d imethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, and the mechanism of induction were investigated in terms of cytoskeletal c hanges. DMAA caused mitotic arrest and concomitant induction of multinuclea ted 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 demonstrate d that the cells escaped from metaphase with ameboid behaviour and pseudopo dia, but they did not divide into daughter cells, thereby resulting in mult inucleated cells. During the post-mitotic incubation in the presence of DMA A, the cells did not proliferate but retained their capacity to synthesize DNA. DMAA caused disappearance of the microtubule network in interphase cel ls, but did not influence the organization of actin stress fibres. Furtherm ore, DMAA caused aberrations of mitotic microtubules, such as tripolar or q uadripolar spindles and aster-like spindles, in a concentration-dependent m anner. These results suggest that DMAA specifically acted on the microtubul es and that multinucleated cells appeared when cells with aberrant spindles escaped from metaphase to advance the cell cycle and the nuclear membranes were regenerated. (C) 1999 Elsevier Science Ltd. All rights reserved.