Co-exposure of sodium arsenite and uranyl acetate differentially alters gene expression in CD3/CD28 activated CD4+ T-cells.
Toxicol Rep
; 8: 1917-1929, 2021.
Article
en En
| MEDLINE
| ID: mdl-34926170
ABSTRACT
Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines. Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 µM and 10 µM), uranyl acetate (3 µM and 30 µM) or a mixture of sodium arsenite and uranyl acetate (1 µM sodium arsenite + 3 µM uranyl acetate). Sodium arsenite induced a dose dependent effect on activation associated gene expression; targeting immune response genes at the lower dose. Increases in oxidative stress gene expression were observed with both sodium arsenite doses. While uranyl acetate alone did not significantly alter activation associated gene expression, the mixture of uranyl acetate with sodium arsenite demonstrated a combined effect relative to sodium arsenite alone. The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the toxicological impact of these mixtures on T-cell activation, function and immune dysregulation.
APC, antigen presenting cell; AUM, abandoned uranium mine; Arsenic; DEG, differentially expressed gene; GCLM, glutamate-cysteine ligase; HMOX1, heme oxygenase 1; IFNγ, interferon gamma; IL-2, interleukin 2; MHC, major histone compatibility complex; Mixture toxicology; NQO1, NAD(P)H quinone dehydrogenase; PCA, principal component analysis; SOD1, super oxide dismutase 1; T-lymphocytes; TCR, T-cell receptor; Th, T-helper; Uranium
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Toxicol Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos