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In vivo tungsten exposure alters B cell development and increases DNA damage in murine bone marrow.
MedLine Citation:
PMID:  23152188     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia (preB-ALL) cluster, however a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following one week, and continued to accumulate thereafter, albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B-cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks exposure, all tungsten groups had a significantly greater percentage of cells in the late pro/large preB developmental stages. DNA damage was increased in both whole marrow and isolated B-cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure, and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.
Authors:
Alexander D R Kelly; Maryse Lemaire; Yoon Kow Young; Jules H Eustache; Cynthia Guilbert; Manuel Flores Molina; Koren K Mann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Div. of Experimental Medicine, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.
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