Studies of selenium and arsenic mutual protection in human HepG2 cells

Kaur, Gurnit; Ponomarenko, Olena; Zhou, Janet R.; Swanlund, Diane P.; Summers, Kelly L.; Dolgova, Natalia V.; Antipova, Olga; Pickering, Ingrid J.; George, Graham N.; Leslie, Elaine M.

doi:10.1016/j.cbi.2020.109162

Title: Studies of selenium and arsenic mutual protection in human HepG2 cells

Journal Article · Sun Jun 07 00:00:00 EDT 2020 · Chemico-Biological Interactions

DOI:https://doi.org/10.1016/j.cbi.2020.109162· OSTI ID:1668071

Kaur, Gurnit ^[1]; Ponomarenko, Olena ^[2]; Zhou, Janet R. ^[1]; Swanlund, Diane P. ^[1]; Summers, Kelly L. ^[2]; Dolgova, Natalia V. ^[2]; Antipova, Olga ^[3]; Pickering, Ingrid J. ^[2]; George, Graham N. ^[2]; Leslie, Elaine M. ^[1]

Univ. of Alberta, Edmonton, AB (Canada)
Univ. of Saskatchewan, Saskatoon, SK (Canada)
Argonne National Lab. (ANL), Argonne, IL (United States)

Hundreds of millions of people worldwide are exposed to unacceptable levels of carcinogenic inorganic arsenic. Animal models have shown that selenium and arsenic are mutually protective through the formation and elimination of the seleno-bis(S-glutathionyl) arsinium ion [(GS)₂AsSe]^-. Consistent with this, human selenium deficiency in arsenic-endemic regions is associated with arsenic-induced disease, leading to the initiation of human selenium supplementation trials. In contrast to the protective effect observed in vivo, in vitro studies have suggested that selenite increases arsenite cellular retention and toxicity. This difference might be explained by the rapid conversion of selenite to selenide in vivo. In the current study, selenite did not protect the human hepatoma (HepG2) cell line against the toxicity of arsenite at equimolar concentrations, however selenide increased the IC₅₀ by 2.3-fold. Cytotoxicity assays of arsenite + selenite and arsenite + selenide at different molar ratios revealed higher overall mutual antagonism of arsenite + selenide toxicity than arsenite + selenite. Despite this protective effect, in comparison to ⁷⁵Se-selenite, HepG2 cells in suspension were at least 3-fold more efficient at accumulating selenium from reduced ⁷⁵Se-selenide, and its accumulation was further increased by arsenite. X-ray fluorescence imaging of HepG2 cells also showed that arsenic accumulation, in the presence of selenide, was higher than in the presence of selenite. These results are consistent with a greater intracellular availability of selenide relative to selenite for protection against arsenite, and the formation and retention of a less toxic product, possibly [(GS)₂AsSe]^-.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: Canadian Institutes of Health Research (CIHR); Univ. of Saskatchewan, Saskatoon, SK (Canada); Natural Sciences and Engineering Research Council of Canada (NSERC); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1668071

Journal Information:: Chemico-Biological Interactions, Vol. 327; ISSN 0009-2797

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Studies of selenium and arsenic mutual protection in human HepG2 cells

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