Document Detail


Arsenic species that cause release of iron from ferritin and generation of activated oxygen.
MedLine Citation:
PMID:  11068869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The in vitro effects of four different species of arsenic (arsenate, arsenite, monomethylarsonic acid, and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) significantly released iron from horse spleen ferritin either with or without the presence of ascorbic acid, a strong synergistic agent. Ascorbic acid-mediated iron release was time-dependent as well as both DMA(III) and ferritin concentration-dependent. Iron release from ferritin by DMA(III)) alone or with ascorbic acid was not significantly inhibited by superoxide dismutase (150 or 300 units/ml). However, the iron release was greater under anaerobic conditions (nitrogen gas), which indicates direct chemical reduction of iron from ferritin by DMA(III), with or without ascorbic acid. Both DMA(V) and DMA(III)) released iron from both horse spleen and human liver ferritin. Further, the release of ferritin iron by DMA(III)) with ascorbic acid catalyzed bleomycin-dependent degradation of calf thymus DNA. These results indicate that exogenous methylated arsenic species and endogenous ascorbic acid can cause (a) the release of iron from ferritin, (b) the iron-dependent formation of reactive oxygen species, and (c) DNA damage. This reactive oxygen species pathway could be a mechanism of action of arsenic carcinogenesis in man.
Authors:
S Ahmad; K T Kitchin; W R Cullen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  382     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-28     Completed Date:  2000-11-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  195-202     Citation Subset:  IM    
Affiliation:
Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenates / toxicity
Arsenic / pharmacokinetics,  toxicity*
Arsenicals / adverse effects
Arsenites / toxicity
Cacodylic Acid / toxicity
Carcinogens / toxicity
Cattle
Ferritins / chemistry,  drug effects*,  metabolism*
Glutathione / metabolism
Horses
Humans
Iron / metabolism*
Kinetics
Methylation
Neoplasms / etiology
Reactive Oxygen Species / metabolism*
Chemical
Reg. No./Substance:
0/Arsenates; 0/Arsenicals; 0/Arsenites; 0/Carcinogens; 0/Reactive Oxygen Species; 124-58-3/monomethylarsonic acid; 15502-74-6/arsenite; 70-18-8/Glutathione; 7439-89-6/Iron; 7440-38-2/Arsenic; 75-60-5/Cacodylic Acid; 7778-39-4/arsenic acid; 9007-73-2/Ferritins

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


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