Document Detail


Arsenite uptake and metabolism by rat hepatocyte primary cultures in comparison with kidney- and hepatocyte-derived rat cell lines.
MedLine Citation:
PMID:  10568694     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Biotransformation by methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) influences inorganic arsenical toxicity, which is often investigated in cultured cells. Arsenic (III) uptake and methylation was assessed in rat hepatocytes in primary culture and in three established rat cell lines (hepatoma-derived McA-RH 7777 cells and H4-II-EC-3 cells, and kidney epithelium-derived NRK-52E cells) to compare their use as model systems for arsenite metabolism. Incubation of all cell types with 0.27, 0.67, 1.33, 2.67, or 6.67 microM As(III) concentrations resulted in concentration-dependent arsenic uptake and biomethylation. Arsenic uptake by the NRK-52E cells was initially slower than that of the other cells, but by 8 h, total uptake was similar in all cell types. At the lowest arsenite concentration, the percentages of total arsenic methylated to MMA and DMA by the hepatocytes and the McA-RH 7777 cells were similar (67 and 66%); methylation by the H4-II-EC-3 cells was somewhat lower (52%), and methylation by the kidney-derived NRK-52E cells was much lower (15%). Total arsenic methylation was inhibited in the cell lines, but not in the hepatocytes, at the highest arsenite concentrations. In all cases, exposure to increased arsenite concentrations inhibited conversion of MMA to DMA much more than it affected the initial methylation step (inorganic arsenite to MMA). These results indicate that rat hepatocytes in primary culture and established rat hepatoma-derived cell lines are similar in their abilities to accumulate and methylate arsenic to MMA and DMA at environmentally relevant arsenic concentrations in the medium. They differed from the kidney epithelium-derived cells, which exhibited substantially lower biomethylation activity.
Authors:
F M Tatum; R D Hood
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  52     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-14     Completed Date:  1999-12-14     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  20-5     Citation Subset:  IM    
Affiliation:
United States Department of Agriculture, National Animal Disease Center, Ames, Iowa 50010, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arsenites / metabolism*
Cell Line
Cells, Cultured
Feasibility Studies
Kidney / cytology,  metabolism*
Liver / cytology,  metabolism*
Male
Methylation
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Arsenites; 15502-74-6/arsenite

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


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