Abstract：
:Glutathione (GSH) plays an important role in the metabolism of arsenite and arsenate by generating arsenic-glutathione complexes. Although dimethylarsinic acid (DMA(V)) is the major metabolite of inorganic arsenicals (iAs) in urine, it is not clear how DMA(V) is produced from iAs. In the present study we report that S-(dimethylarsino)-glutathione (DMA(III)(SG)), a putative precursor of dimethylarsinic acid DMA(V), was unstable in the culture medium without excess GSH and generated volatile substances which were highly cytotoxic for both rat heart microvascular endothelial cells and HL60, a human leukemia cell line. Cytotoxicity of DMA(III)(SG) was higher than that of iAs and its LC(50) value was calculated to be 7.8 microM in the endothelial cells. To our surprise DMA(III)(SG) effectively killed cells in the neighbor wells of the same multi-well dish, indicating that volatile toxic compounds generated from DMA(III)(SG) in the culture medium. High performance lipid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) analyses suggested that the freshly generated volatile compounds dissolved into aqueous solution and formed an unstable arsenic compound and the unstable compound was further converted to DMA(V). These results suggested that DMA(III)(SG) exerts its cytotoxicity by generating volatile arsenicals and is implicated in the metabolic conversion of inorganic arsenicals into DMA(V), a major final metabolite of inorganic arsenicals in most mammals.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Hirano S,Kobayashi Ydoi
10.1016/j.tox.2006.07.009subject
Has Abstractpub_date
2006-10-03 00:00:00pages
45-52issue
1-2eissn
0300-483Xissn
1879-3185pii
S0300-483X(06)00450-1journal_volume
227pub_type
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