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Investigating a 3‐step leukemogenic hypothesis in C57BL/6 mice: tungsten, RSV and hypoxia
Author(s) -
Fastje Cynthiha D.,
Harper Kevin,
Terry Chad,
Wong Simon S.,
Witten Mark L.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.565.13
Subject(s) - neutrophilia , immunology , biology , saliva , leukocytosis , microarray , transcriptome , gene , gene expression , genetics , biochemistry
Significantly elevated concentrations of tungsten have been demonstrated in the atmospheric particulate matter in multiple communities experiencing elevated rates of childhood leukemia, but not in their respective control communities. Prenatal exposure to sodium tungstate in C57BL/6 mice (2208mg/kg/day via aerosol and/or 0.0994mg/kg/day via drinking water) significantly decreased the transcriptome expression of Dmbt1, a protein which functions to aggregate bacteria and viruses in lung mucosa and saliva. Additionally, analysis of gene microarray data produced a significant network associated with hematological/immunological disease focused on genes involved in viral defense. We hypothesize that the etiology of environmentally‐induced leukemia is in utero exposure to metals such as tungsten (W) which may increase susceptibility to viral influences, post‐natal exposure to Respiratory Syncytial Virus (RSV), and triggered by a hypoxic event. End measures include qRT‐PCR of RSV genes F & G during the fastigium of the infection, RT2‐PCR for genes associated with immunological function, and a complete blood count with a differential. Mice in the W/RSV/Hypoxia group developed neutrophilia post‐hypoxic challenge and at five months developed lymphocytosis contributing to leukocytosis. Supported by EPA Grant EM‐96963201