Document Detail


In vitro cytotoxic and genotoxic effects of diphenylarsinic acid, a degradation product of chemical warfare agents.
MedLine Citation:
PMID:  15451309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diphenylarsinic acid [DPAs(V)], a degradation product of diphenylcyanoarsine or diphenylchloroarsine, both of which were developed as chemical warfare agents, was investigated in terms of its capacity to induce cytotoxic effects, numerical and structural changes of chromosomes, and abnormalities of centrosome integrity and spindle organizations in conjunction with the effects of glutathione (GSH) depletion. DPAs(V) had toxic effects on cultured human hepatocarcinoma HepG2 cells at concentrations more than 0.5 mM. Depletion of GSH reduced the toxic effects of DPAs(V) as well as dimethylarsinic acid [DMAs(V)] toxicity, while toxicity by arsenite [iAs(III)] was enhanced. Exogenously added sulfhydryl (SH) compounds, such as dimercapropropane sulfonate (DMPS), GSH, and dithiothreitol (DTT), enhanced the toxic effects of DPAs(V) while they suppressed iAs(III) toxicity. DPAs(V) caused an increase in the mitotic index, and also structural and numerical changes in chromosomes in V79 Chinese hamster cells. Abnormality of centrosome integrity in mitotic V79 cells and multipolar spindles was also induced by DPAs(V) in a time- and concentration-dependent manner. These results suggested that highly toxic chemicals were generated by the interaction of DPAs(V) with SH compounds. Moreover, enhancements of toxicity by a combination of DPAs(V) and SH compounds suggested a risk in the use of SH compounds as a remedy for intoxication by diphenylarsenic compounds. Investigations on the effects of SH compounds on animals intoxicated with DPAs(V) are warranted.
Authors:
Takafumi Ochi; Toshihide Suzuki; Hideo Isono; Toshikazu Kaise
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  200     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-28     Completed Date:  2004-11-19     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  64-72     Citation Subset:  IM    
Affiliation:
Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. tkfmochi@pharm.teikyo-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenicals
Cell Line, Tumor
Cell Survival
Cells, Cultured
Centrosome / drug effects,  ultrastructure
Chemical Warfare Agents / toxicity*
Chromosomes / drug effects,  ultrastructure
Cricetinae
DNA / biosynthesis
Fluorescent Antibody Technique
Glutathione / metabolism
Humans
Male
Microtubules / drug effects,  ultrastructure
Mitotic Index
Mitotic Spindle Apparatus / drug effects,  ultrastructure
Mutagens*
Sulfhydryl Compounds / toxicity
Tubulin / metabolism
Chemical
Reg. No./Substance:
0/Arsenicals; 0/Chemical Warfare Agents; 0/Mutagens; 0/Sulfhydryl Compounds; 0/Tubulin; 0/diphenylarsinic acid; 70-18-8/Glutathione; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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