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). Pre-incubation with 100-mu-M GSH for 24 h partially prevented the growth inhibition caused by 12.6-mu-M selenite. Pre-incubation with 100-mu-M GSH for 48 h completely prevented the growth inhibition caused by 12.6-mu-M 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-mu-M) 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 pre-incubation 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.