Ochi T, Nakajima F, Fukumori N
Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Arch Toxicol. 1998 Sep;72(9):566-73. doi: 10.1007/s002040050544.
Changes in cytoskeletal organization of cultured V79 cells exposed to arsenite and dimethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, and related changes, such as mitotic arrest and induction of multinucleated cells, were investigated in comparison with their effects on DNA synthesis. DMAA caused mitotic arrest and induction of multinucleated cells with a delay of 12 h relative to the mitotic arrest. By contrast, arsenite at equitoxic concentrations to DMAA was less effective than DMAA in causing mitotic arrest and in inducing multinucleated cells. Post-mitotic incubation of cells arrested in metaphase by 6 h incubation with 10 mM DMAA showed that the incidence of multinucleated cells increased conversely with a rapid decrease in metaphase cells. This suggests that metaphase-arrested cells can escape from metaphase, resulting in the appearance of multinucleated cells. The mitotic arrest caused by DMAA was accompanied by disruption of the microtubule network. By contrast, both arsenite and DMAA did not cause disorganization of actin stress fibers even when incubated at concentrations that caused a marked retardation of cell growth. Cells exposed to arsenite for 6 h showed marked inhibition of DNA synthesis, whereas inhibition by DMAA was not observed. When incubation was prolonged by 18 h, the arsenite-induced inhibition of DNA synthesis was mitigated. By contrast, inhibition of DNA synthesis by DMAA occurred in parallel with an increase in the population of mitotic cells. These results suggest that DMAA caused growth retardation and morphological changes via disruption of the microtubule network, and that arsenite-induced retardation of cell growth and inhibition of DNA synthesis were not attributable to the cytoskeletal changes.
研究了暴露于亚砷酸盐和二甲基砷酸（DMAA，无机砷的甲基化衍生物）的培养V79细胞的细胞骨架组织变化，以及相关变化，如有丝分裂停滞和多核细胞诱导，并将其与对DNA合成的影响进行了比较。DMAA导致有丝分裂停滞和多核细胞诱导，相对于有丝分裂停滞延迟12小时。相比之下，与DMAA等毒性浓度的亚砷酸盐在引起有丝分裂停滞和诱导多核细胞方面不如DMAA有效。用10 mM DMAA孵育6小时使细胞停滞在中期后进行有丝分裂后孵育，结果表明多核细胞的发生率与中期细胞的快速减少呈相反增加。这表明中期停滞的细胞可以从中期逃脱，导致多核细胞出现。DMAA引起的有丝分裂停滞伴随着微管网络的破坏。相比之下，亚砷酸盐和DMAA即使在导致细胞生长明显迟缓的浓度下孵育，也不会引起肌动蛋白应激纤维的紊乱。暴露于亚砷酸盐6小时的细胞显示出明显的DNA合成抑制，而未观察到DMAA的抑制作用。当孵育延长18小时时，亚砷酸盐诱导的DNA合成抑制得到缓解。相比之下，DMAA对DNA合成的抑制与有丝分裂细胞群体的增加同时发生。这些结果表明，DMAA通过破坏微管网络导致生长迟缓并引起形态变化，并且亚砷酸盐诱导的细胞生长迟缓及DNA合成抑制并非归因于细胞骨架变化。
