Kuchan M J, Milner J A
Division of Nutritional Sciences, University of Illinois, Urbana 61801.
Cancer Res. 1992 Mar 1;52(5):1091-5.
The present studies demonstrate that the ability of supplemental selenite to alter the in vitro growth of canine mammary tumor cell line 13 was dependent on the quantity and duration of selenium exposure and on the culture density. Exposure to 3.2 microM selenite did not significantly alter growth but led to an increase in intracellular glutathione (GSH). The severity of growth inhibition between 3.2 and 9.6 microM selenite was dependent on the duration of exposure and culture density. The toxicity of selenite generally increased as the culture density increased. Likewise, changes in intracellular GSH were dependent on the quantity and duration of selenite exposure and the culture density. Depressing intracellular GSH by increasing the culture density or by incubating with buthionine sulfoximine; a specific inhibitor of gamma-glutamyl cysteine synthetase, increased the severity of growth inhibition caused by selenite and markedly increased cellular retention of selenium. Nevertheless, marked cellular retention of selenium did not occur until growth was inhibited by more than 50%. The present studies revealed that the log of the molar ratio of GSH to selenium correlated negatively with the severity of growth inhibition (P less than 0.0001). These studies suggest that cellular toxicity of selenite is dependent on the regulation of the GSH:selenium ratio. An inability to regulate this ratio likely leads to the accumulation of toxic seleno compounds.
目前的研究表明，补充亚硒酸盐改变犬乳腺肿瘤细胞系13体外生长的能力取决于硒暴露的量和持续时间以及培养密度。暴露于3.2微摩尔亚硒酸盐不会显著改变生长，但会导致细胞内谷胱甘肽（GSH）增加。3.2至9.6微摩尔亚硒酸盐之间生长抑制的严重程度取决于暴露持续时间和培养密度。亚硒酸盐的毒性通常随着培养密度的增加而增加。同样，细胞内GSH的变化取决于亚硒酸盐暴露的量和持续时间以及培养密度。通过增加培养密度或与丁硫氨酸亚砜亚胺（γ-谷氨酰半胱氨酸合成酶的特异性抑制剂）孵育来降低细胞内GSH，会增加亚硒酸盐引起的生长抑制的严重程度，并显著增加细胞对硒的保留。然而，直到生长被抑制超过50%才会出现明显的细胞对硒的保留。目前的研究表明，GSH与硒的摩尔比的对数与生长抑制的严重程度呈负相关（P小于0.0001）。这些研究表明，亚硒酸盐的细胞毒性取决于GSH:硒比例的调节。无法调节该比例可能导致有毒硒化合物的积累。
