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]⁻.

全球数以亿计的人暴露于令人难以接受的致癌无机砷水平。动物模型表明，硒和砷通过形成和消除硒代双（S-谷胱甘肽）砷离子[（GS）₂ AsSe] ^-相互保护。与此相一致，砷流行地区的人体硒缺乏与砷引起的疾病有关，从而引发了人体硒补充试验的启动。与体内观察到的保护作用相反，体外研究表明，亚硒酸盐会增加亚砷酸盐的细胞保留和毒性。亚硒酸盐快速转化为硒化物可以解释这种差异体内。在当前的研究中，亚硒酸盐不能保护人肝癌（HepG2）细胞系免受亚砷酸盐在等摩尔浓度下的毒性作用，但是亚硒酸盐使IC ₅₀升高了2.3倍。在不同的摩尔比下，亚砷酸盐+亚硒酸盐和亚砷酸盐+硒化物的细胞毒性试验显示，亚砷酸盐+硒化物的总体总体拮抗作用高于亚砷酸盐+亚硒酸盐。尽管有这种保护作用，与⁷⁵硒硒相比，悬浮的HepG2细胞从减少的⁷⁵硒中富集硒的效率至少高3倍。硒硒，其积累进一步被亚砷酸盐增加。HepG2细胞的X射线荧光成像还显示，在存在硒化物的情况下，砷的积累要高于在存在硒酸盐的情况下。这些结果与相对于亚硒酸盐保护亚砷酸盐的硒化物具有更高的细胞内利用率，以及毒性较低的产物，可能是[（GS）₂ AsSe] ^-的形成和保留相一致。