INFLUENCE OF 2,3-DIMERCAPTOPROPANOL AND OTHER SULFUR-COMPOUNDS ON OXOPHENYLARSINE-MEDIATED INHIBITION OF GLUCOSE-UPTAKE IN MDCK CELLS

Trivalent monosubstituted organoarsenicals, e.g., oxophenylarsine (PhA sO), exert various detrimental effects on mammalian cells. In addition to their well known interference with pyruvate and ketoglutaric acid oxidation, the effect on other cellular functions such as uptake of gl ucose may contribute to their acute toxicity. Different effects of PhA sO on insulin-stimulated and insulin-independent uptake of hexoses in various tissues have been reported. It has been shown previously that PhAsO inhibits the stereospecific uptake of glucose in MDCK cells. In this work, the insulin dependence of glucose uptake in these cells and the effects of 2,3-dimercaptopropanol (BAL), dithiothreitol (DTT) and 2-mercaptoethanol (ME) on PhAsO-induced inhibition of glucose uptake were investigated. A 200 mu mol l(-1) concentration of insulin had no measurable effect on cellular C-14 accumulation from D-[6-C-14]glucose , indicating an insulin-independent hexose transport system. In the pr esence of 2 mu mol l(-1) of PhAsO, glucose uptake was lowered to less than 50% of controls within 30 min, Greater inhibition was observed wi th higher concentrations of PhAsO, but cell viability as assessed by f ormazan formation started to decrease at concentrations greater than o r equal to 5 mu mol l(-1), especially after longer exposure times. Whe n BAL was added in a ten-fold molar excess 30 min after beginning incu bation with PhAsO (2 mu mol l(-1)), virtually complete recovery of inh ibited glucose uptake occurred within 10 min after addition. ME at up to a 100-fold molar excess over arsenic had no influence on the inhibi tion of glucose uptake within 120 min after addition. DTT only partial ly reversed inhibited glucose uptake at a 100-fold molar excess over P hAsO. The findings suggest that PhAsO inhibits insulin-independent, st ereospecific uptake of hexoses in MDCK cells and that this inhibition is effectively counteracted by dithiol compounds, vicinal dithiols bei ng most effective.