Document Detail

Induction of genotoxic damage is not correlated with the ability to methylate arsenite in vitro in the leukocytes of four mammalian species.
MedLine Citation:
PMID:  12112384     Owner:  NLM     Status:  MEDLINE    
Arsenic is a natural drinking water contaminant that impacts the health of large populations of people throughout the world; however, the mode or mechanism by which arsenic induces cancer is unclear. In a series of in vitro studies, we exposed leukocytes from humans, mice, rats, and guinea pigs to a range of sodium arsenite concentrations to determine whether the lymphocytes from these species showed differential sensitivity to the induction of micronuclei (MN) assessed in cytochalasin B-induced binucleate cells. We also determined the capacity of the leukocytes to methylate arsenic by measuring the production of MMA [monomethylarsinic acid (MMA(V)) and monomethylarsonous acid (MMA(III))] and DMA [dimethylarsinic acid (DMA(V)) and dimethylarsonous acid (DMA(III))]. The results indicate that cells treated for 2 hr at the G(0) stage of the cell cycle with sodium arsenite showed only very small to negligible increases in MN after mitogenic stimulation. Treatment of actively cycling cells produced induction of MN with increasing arsenite concentration, with the human, rat, and mouse lymphocytes being much more sensitive to MN induction than those of the guinea pig. These data gave an excellent fit to a linear model. The leukocytes of all four species, including the guinea pig (a species previously thought not to methylate arsenic), were able to methylate arsenic, but there was no clear correlation between the ability to methylate arsenic and the induction of MN.
B Peng; R Sharma; M J Mass; A D Kligerman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  39     ISSN:  0893-6692     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2002  
Date Detail:
Created Date:  2002-07-11     Completed Date:  2002-08-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  323-32     Citation Subset:  IM    
Environmental Carcinogenesis Division MD-68, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
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MeSH Terms
Arsenites / toxicity*
Cells, Cultured
Cytochalasin B / metabolism
G0 Phase
Guinea Pigs
Leukocytes / drug effects*
Regression Analysis
Sodium Compounds / toxicity*
Reg. No./Substance:
0/Arsenites; 0/Sodium Compounds; 13768-07-5/sodium arsenite; 14930-96-2/Cytochalasin B

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