Document Detail

Microbial metabolite of dimethylarsinic acid is highly toxic and genotoxic.
MedLine Citation:
PMID:  15276414     Owner:  NLM     Status:  MEDLINE    
Dimethylarsinic acid [DMA, (CH(3))(2)AsO(OH)] causes cancer in the urinary bladder of rats. However, its mechanism of cancer or the ultimate carcinogenic form is not yet known. Rats administered dimethylarsinic acid excrete three unknown arsenic compounds (termed M-1, M-2, and M-3) in urine or feces, and these compounds are presumed to be produced by intestinal bacteria. Escherichia coli A3-6 isolated from a rat yielded two unknown arsenic compounds (M-2 and M-3) from dimethylarsinic acid and M-1 from trimethylarsine oxide (TMAO) in the presence of cysteine (Cys). Contents of M-2 and M-3 varied with cysteine concentration. The cytotoxicity and genotoxicity of the bacteria-free solution of dimethylarsinic acid or trimethylarsine oxide metabolized by E. coli A3-6 were studied using V79 cells. Dimethylarsinic acid (1 mM) metabolized by E. coli A3-6 in the presence of cysteine (1 mM) was highly cytotoxic (50% survival reduction concentration; 2.1 microM As) in V79 cells, and the toxic substance appeared to be M-2. The metabolite solution (at 2.5-10 microM total As) induced c-mitosis and tetraploids, and caused mitotic arrest, since it increased mitotic cells at the cytotoxic dose. The metabolite solution also significantly increased sister chromatid exchange (SCE) and chromosomal aberrations, most of which were chromatid gaps and chromatid breaks. A3-6 converted 96.1% of trimethylarsine oxide to M-1 in the presence of cysteine. This metabolite solution did not exhibit cytotoxicity or genotoxicity. The reported M-2 concentration in urine of rats administered levels of DMA via drinking water known to cause bladder tumors was sufficient to exhibit cytotoxic and genotoxic effects in urinary bladder. Thus, we hypothesize that intestinal bacteria play an important role in carcinogenicity of dimethylarsinic acid.
Koichi Kuroda; Kaoru Yoshida; Mieko Yoshimura; Yoko Endo; Hideki Wanibuchi; Shoji Fukushima; Ginji Endo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  198     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-27     Completed Date:  2004-09-14     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:  345-53     Citation Subset:  IM    
Department of Preventive Medicine and Environmental Health, Osaka City University Medical School, 545-8585, 1-4-3 Asahi-machi, Abeno, Osaka, Japan.
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MeSH Terms
Arsenicals / metabolism*
Cacodylic Acid / metabolism,  toxicity*
Cells, Cultured
Chromosome Aberrations / drug effects
Escherichia coli / drug effects,  metabolism*
Herbicides / metabolism,  toxicity*
Mutagens / metabolism,  toxicity*
Sister Chromatid Exchange / drug effects
Reg. No./Substance:
0/Arsenicals; 0/Herbicides; 0/Mutagens; 75-60-5/Cacodylic Acid

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