It has been proposed that some selenium (Se) compounds act as prooxidants in glutathione (GSH) replete cells, since they are metabolized to form the catalytic species GSSe-, which can oxidize GSH and generate superoxide. Different Se compounds may have varying toxicity, based upon their ability to interact with GSH in cells, tumor cells usually having higher GSH levels than normal ones. The present study was designed examine this differential toxicity in a cell culture system using normal primary human keratinocytes, from neonatal, 19, 38 and 63 year old subjects, and squamous cell carcinoma cells (SCCs), supplemented for 24 hours at 50% confluency with selenite (5-50 μg Se/mL), selenocystamine (SeC; 5-250 μg Se/mL), and selenomethionine (SeM; 5-250 μg Se/mL). Cell viability for all treatments and negative controls was assessed after 24 hours by trypan blue dye exclusion. There was no effect of age. Viability decreased with treatment dose for SeC and selenite, but SeM had no effect on viability at the doses tested. The relative toxicity of the Se compounds was selenite > SeC ⋙ SeM, with SCCs more vulnerable than normal keratinocytes. The toxicity appeared to be related to the ability of the compound to deplete cellular GSH. These data may provide some insight into the mechanism of protection by selenite against experimental skin cancer.
|State||Published - 1997|