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The selenium salt selenite (Se[O.sub.3.sup.2-]) is cytotoxic in low to moderate concentrations, with a remarkable specificity for cancer cells resistant to conventional chemotherapy. Our data show that selenium uptake and accumulation, rather than intracellular events, are crucial to the specific selenite cytotoxicity observed in resistant cancer cells. We show that selenium uptake depends on extracellular reduction, and that the extracellular environment is a key factor specific to selenite cytotoxicity. The extracellular reduction is mediated by cysteine, and the efficacy is determined by the uptake of cystine by the [x.sub.c.sup.-] antiporter and secretion of cysteine by multidrug resistance proteins, both of which are frequently over-expressed by resistant cancer cells. This mechanism provides molecular evidence for the existence of an inverse relationship between resistance to conventional chemotherapy and sensitivity to selenite cytotoxicity, and highlights the great therapeutic potential in treating multidrug-resistant cancer. drug resistance | pharmacology | selenium

The toxicity of selenite at high concentrations in biological organisms is caused by the generation of free radicals during its metabolism. In Rhodobacter sphaeroides, selenite is transported into cells by a polyol transporter.

The bioavailability of selenate and selenite were compared in cattle, sheep and horses. There were only minor differences between the two forms used when serum, skeletal muscle and liver selenium (Se) as well as serum glutathione peroxidase activities were measured. The serum Se level increased with the duration of Se supplementation. A dietary supplementation of .3 mg of Se per kilogram of dietary dry matter of either selenate or selenite forms can support normal serum levels of Se in the three species.