Petrick et al. |
2009 |
Sprague-Dawley rat |
Both |
Lung physiology |
0, 500 ppb |
In utero exposure to As results in decreased weight of fetal rat lung. Genes and proteins associated with cell motility, cytoskeleton, and adhesion were also altered in the fetal rat lung. |
Patra et al. |
2013 |
Black Bengal Goat(s) |
Female |
Humoral immunity |
0, 2 mg/kg BW |
Serum IgG, hemoglobin, total erythrocyte count, and total leukocyte counts were all significantly reduced in arsenic-exposed animals. Bone marrow cells of arsenic-exposed goats were found to have higher caspase-3 activity and increased DNA nicking. |
Nain et al. |
2012 |
Wistar rat |
Male |
Humoral immunity |
0, 400, 4,000, 40,000 ppb |
Secondary antibody (IgG) production against keyhole limpet hemocyanin antigen was decreased with increasing arsenic exposure, while neutrophil oxidative burst potential was unaffected. |
Ramsey et al. |
2013a |
C57BL/6 mice |
Both |
Humoral and cell-mediated immunity |
0, 10, 100 ppb |
Prenatal exposure of C57BL/6 mice to 100 ppb of arsenic resulted in increased susceptibility of offspring to influenza A infection at 1 week of life. |
Ramsey et al. |
2013b |
C57BL/6 mice |
Both |
Humoral and cell-mediated immunity |
0, 100 ppb |
Prenatal exposure of C57BL/6 mice to 100 ppb of arsenic was correlated with smaller lung size and reduced pulmonary function in pups. Genes involved in mucociliary clearance and innate immunity were also upregulated in pups born to arsenic-exposed dams. |
Kozul et al. |
2009 |
C57BL/6 mice |
Male |
Humoral and cell-mediated immunity |
0, 100 ppb |
Treatment of adult male C57BL/6J mice with 100 ppb As resulted in reduced host immunity against influenza A and increased viremia. |
Ezeh et al. |
2016 |
C57BL/6 mice; 2E8 cell line |
Male |
Cell-mediated immunity |
0, 5, 50, 500 nM As3+ or MMA3+
|
Authors found that the STAT5 signaling pathway was suppressed after exposure of C57BL/6 primary bone marrow cells to low-dose As3+ or MMA3+ and that STAT5 signaling was suppressed in 2E8 cells only with low doses of MMA3+, revealing that this arsenic metabolite is likely responsible for early lymphocyte dysregulation and toxicity, since 2E8 cells lack the AS3MT enzyme needed to metabolize As3+. |
Xu et al. |
2016a |
C57BL/6 mice; D1 cell line |
Male |
Cell-mediated immunity |
0, 5, 50, 500 nM As3+ or MMA3+
|
The authors cultured primary mouse thymocytes and D1 cells at various concentrations of As3+ and MMA3+ and assessed the effects on the STAT5 signaling pathway, an important pathway in the development of pro-B cell and double-negative T cells. They found that both As3+ and MMA3+ suppress Jak1 and Jak3 phosphorylation as well as STAT5 signaling (a downstream phosphorylation target of Jak kinases) and that MMA3+ exposure results in decreased IL-7R (an important downstream developmental receptor of STAT5 signaling) expression on D1 cells. |
Xu et al. |
2016b |
C57BL/6 mice |
Male |
Cell-mediated immunity |
0, 100, 500 ppb As3+
|
The authors exposed mice to varying concentrations of trivalent inorganic arsenic for 30 days, then assessed arsenic speciation and DNA damage in the thymus, bone marrow, and spleen. They found dose-dependent increases in MMA3+ in both the spleen and thymus, but no correlation between arsenic dose and MMA3+ concentration in the spleen. Additionally, dose-dependent increases in DNA damage were observed in the thymus and bone marrow. |
Cho et al. |
2012 |
C57B/6 mice |
Female |
Cell-mediated immunity |
0, 0.03, 0.06, 0.13, 0.25, 0.5, 1.0, 2.0 μM |
Splenocytes were isolated from young adult (2 months) or aged (24–26 months) female mice and co-cultured with varying concentrations of sodium arsenite and a mitogen or anti-CD3 antibody. In young mice, increasing doses of arsenic were associated with decreasing IFN-γ production and decreased IL-10 production in aged mice when co-culture with Con A. |
Soto-Peña and Vega |
2008 |
CD57BL6N mice |
Male |
Cell-mediated immunity |
0, 10, 100, 1000 ppb |
Young adult male mice were gavaged daily with varying doses of dissolved sodium arsenite for 30 days. Spleens were then collected. The investigators found that increasing concentrations of arsenic were associated with reduced splenic Th populations along with a reduced CD4+/CD8+ ratio and a resulting increase in the proportion of splenic CD11b+ cells. Increasing arsenic dose was also related to decreases in lymphocyte proliferation in response to co-culture with a mitogen, which may be related to altered lck kinase phosphorylation kinetics. |
Conde et al. |
2007 |
C57BL/6 mice |
Female |
Cell-mediated immunity |
0, 1, 10 μM |
Mononuclear splenocytes were isolated from young adult female mice and cultured with varying sodium arsenite concentrations. Proliferation, ERK phosphorylation, IL-2 mRNA expression, and secretion were measured. Increasing arsenic concentrations were associated with reduced IL-2 expression, secretion, and mononuclear cell proliferation in response to PHA. The highest concentration of arsenic exposure was found to inhibit ERK1/2 phosphorylation, while both concentrations of arsenic studied reduced the total number of splenic CD8+ cells, while leaving CD4+ cells unaffected. |
Patterson et al. |
2004 |
Balb/c mice |
Female |
Cell-mediated immunity |
0, 50,000 ppb |
Treatment of female mice with 50,000 ppb arsenic via drinking water for 4 weeks resulted in reduced delayed-type contact hypersensitivity, circulating neutrophils, and immune cell proliferation as measured by the local lymph node assay as well as an in vitro lymphoproliferation assay. This study also found a reduction in the recruitment of macrophages to the peritoneal cavity, while no effect was seen in the baseline number of macrophages present in the BALF of arsenic-exposed mice when compared with controls. |
Goytia-Acevedo et al. |
2003 |
C57B/6 mice |
Female |
Cell-mediated immunity |
1, 10, 100, 1000nM |
T lymphocytes were isolated from young adult female mice and co-cultured with mitogens PHA or Con A. Authors found that at the highest doses of sodium arsenite, T lymphocytes underwent less mitogen-stimulated proliferation when pretreated (PHA and Con A) or simultaneously cultured (PHA only) with sodium arsenite. |