Influence of supplemental glutathione on selenite-mediated growth inhibition of canine mammary cells.

Present studies show the in vitro addition of glutathione (GSH) can significantly alter selenite induced growth inhibition of mammary tumor cell line 13 (CMT-13). Preincubation with 100 microM GSH for 24 h partially prevented the growth inhibition caused by 12.6 microM selenite. Pre-incubation with 100 microM GSH for 48 h completely prevented the growth inhibition caused by 12.6 microM selenite. In marked contrast, simultaneous addition of GSH and selenite dramatically increased the severity of selenite-mediated growth inhibition and resulted in cell death. Exposure to selenite (12.6 microM) increased intracellular GSH throughout the 3 day incubation period. Addition of GSH to the medium also led to an approximate 25% increase in intracellular GSH that persisted for 72 h. Cellular retention of selenium following selenite supplementation was decreased up to 70% by GSH preincubation yet increased markedly (greater than or equal to 240%) by the simultaneous addition of GSH and selenite. The rate of selenite uptake was not consistently altered by GSH pretreatment. However, the simultaneous addition of GSH and selenite resulted in a dramatically increased rate of selenium uptake. These data indicate that extracellular GSH can alter the toxicity of supplemental selenite. The protective effect of GSH pre-incubation against selenite toxicity appears to relate to altered selenium retention.