SODIUM ARSENITE INDUCES CHROMOSOME ENDOREDUPLICATION AND INHIBITS PROTEIN PHOSPHATASE-ACTIVITY IN HUMAN FIBROBLASTS

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separa tion was studied in human skin fibroblasts (HFW). Human fibroblasts we re arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress i nto G2 phase. Treatment of the G2-enriched HFW cells with sodium arsen ite (0-200 mu M) resulted in arrest of cells in the G2 phase, interfer ence with mitotic division, inhibition of spindle assembly, and induct ion of chromosome endoreduplication in their second mitosis. Sodium ar senite treatment also inhibited the activities of serine/threonine pro tein phosphatases and enhanced phosphorylation levels of a smell heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. (C) 1995 Wiley-Liss , Inc.