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Dimethylarsinic acid targets tubulin in mitotic cells to induce abnormal spindles
Author(s) -
Kawata Hiroko,
Kuroda Koichi,
Endo Yoko,
Endo Ginji
Publication year - 2001
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.212
Subject(s) - tubulin , chemistry , multipolar spindles , mitosis , chinese hamster , microtubule , metaphase , colchicine , cell cycle , microbiology and biotechnology , vinblastine , spindle apparatus , biochemistry , cell , cell division , in vitro , biology , genetics , chromosome , chemotherapy , gene
Dimethylarsinic acid (DMA) is the most effective inducer of cell‐cycle disruption among the arsenic compounds and their metabolites. The present study was conducted to gain further insight into cell‐cycle disruption induced by DMA. The inhibition of cell proliferation and the mitotic arrest induced by DMA were significant and dose‐dependent in Chinese hamster V79 cells and the two seemed to be closely related. At less than 140 µ M the DMA did not inhibit the proliferation of cells, but it significantly induced mitotic arrest. An indirect immunofluorescence assay using anti‐α‐tubulin antibodies revealed that DMA induced the formation of abnormal spindles in the metaphase cells even at 350 µ M with 5 h of treatment. At 1.4 m M DMA no metaphase cells could form a definite spindle structure. The spindle figures were similar to those induced by colchicine (125 n M ) or vinblastine (110 n M ), major antimitotic agents. In DMA‐treated interphase cells, the microtubule networks were indistinguishable from those of normal cells. With the tubulin‐assembly assay estimated by turbidity, DMA at less than 200 µ M suppressed tubulin assembly in a dose‐dependent manner, whereas at more than 700 µ M it enhanced tubulin polymerization remarkably with or without addition of excess guanosine‐5′‐triphosphate. According to the above findings, we discussed the possibility that DMA, a primary metabolite of inorganic arsenic in mammals, is related to arsenic carcinogenicity. Copyright © 2001 John Wiley & Sons, Ltd.