The importance of glucose metabolism in the hypoxic cytotoxicity of Misonidazole

The authors are investigating the mechanism of inhibition of glucose metabolism and its role in the hypoxic cytotoxicity of Misonidazole (Miso). Preincubation of hypoxic exponential EMT6/Ro cells with Miso and 5.5 mM glucose containing media caused a time-dependent inhibition of both glucose consumption and lactate formation. This inhibition began after 90 min, 45 min, and 15 min preincubation with 1mM, 2.5mM, and 5mM Miso respectively. The inhibition closely correlated with the kinetics and extent of decreased viability of these cells as measured by dye exclusion and colony forming efficiency. Miso does not inhibit glucose transport in these phloretin-sensitive cells. Transport was measured by the uptake of 3-0-methyl-D-glucose, a non-metabolized glucose analog. The initial rate was determined to be the same (1.66 +- 0.18 nmoles cell/second at 250C)