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Prenatal Exposure to Tungstate/Arsenite May Increase Susceptibility to Childhood Leukemia
Author(s) -
Fastje Cynthia D.,
Vargas Jason E.,
Wong Simon S.,
Witten Mark L.
Publication year - 2008
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.22.1_supplement.898.34
Subject(s) - in utero , biology , wnt signaling pathway , transcriptome , offspring , andrology , leukemia , microarray , spleen , fetus , immunology , medicine , gene expression , gene , pregnancy , genetics
Two concurrent, childhood leukemia clusters have been identified in the Southwestern U.S. at Fallon, NV and Sierra Vista, AZ. Using advances in medical geology, we have identified tungsten (W) and arsenic (As) as potentially relevant to leukemogenesis and utilized Affymetrix 430A 2.0 mouse microarray and real time RT‐PCR of the gene, Deleted in Malignant Brain Tumors 1 (DMBT1), to ascertain transcriptome‐expression in spleen tissue collected from 4‐week old C57BL/6 mouse pups (N=6–8/group/gender) exposed in utero to W, As, W/As and longitudinal controls at 20% of the normalized exposure a human mother would receive during gestation at mean environmental concentrations. Significantly altered pathways for in utero exposure to W/As includes Mek/Erk/Wnt pathways, antigen presentation and processing pathways, and cytokine interactions involving lymphocytic signaling. Additionally, significantly elevated genes associated with spermatogenesis were noted. Prenatal exposure to W was found to be associated with a 37 ± 1.2‐fold (p=0.012) decrease in DMBT1 expression in mice expressing DMBT1 at high levels. Histological examination of testicular tissue from sires exposed to W during spematogenesis showed a 50% vacancy rate of the seminiferous tubules. W/As prenatal‐exposure may be leukemogenic through increased susceptibility to viruses. Exposure to W may also be associated with reproductive disease. Supported by OAFSR/EPA