INFLUENCE OF GLUCOSE ON THE TOXICITY OF OXOPHENYLARSINE IN MDCK CELLS

Trivalent arsenicals like oxophenylarsine (PhAsO) inhibit cellular pyr uvate dehydrogense, thus leading to a drop of acetylCoA formation and a slowdown of the citric acid cycle. Glucose may protect cells from ar senic toxicity, because increased glycolysis may prevent fatal shortag e of ATP. On the other hand, PhAsO has been shown to inhibit glucose u ptake in Madin-Darby canine kidney (MDCK) cells. We have investigated the effect of PhAsO on viability, ATP levels and glucose uptake of MDC K cells in the presence of normal (5 mmol/l) and low (0.01 mmol/l) glu cose concentrations. At normal as well as at low glucose concentration s, cell viability as assessed by formazan formation was not affected b y PhAsO concentrations up to 2 mu mol/l within 3 h of observation. At higher PhAsO concentrations viability was diminished earlier and more pronounced in the presence of low glucose concentrations. 10 mu mol/l PhAsO induced a drastic drop of ATP within 30 min which was followed b y an almost complete loss of viable cells after 180 min in the presenc e of low glucose concentrations, while at normal glucose levels no inf luence on ATP contents or on cell viability was detected within 60 min of incubation. On the other hand, glucose uptake, determined as C-14 accumulation by cells incubated for 10 min with D-[6-C-14]-glucose, wa s inhibited by PhAsO at low as well as at normal glucose concentration s in a dose dependent manner. At normal glucose concentrations, howeve r, basal uptake was higher (57 nmol/mg protein) and half-maximum inhib ition (IC50) was shifted to higher PhAsO concentrations (2 x 10(-4) mo l/l) than at low glucose levels (basal uptake: 1.6 nmol/mg protein; IC 50: 5 X 10(-5) mol/l). It is concluded that 1) in PhAsO-exposed MDCK c ells different uptake mechanisms operate in high and low glucose state s and 2) that glucose exerts a beneficial effect on the toxicity of Ph AsO in these cells.