title: Decreased hypoxic toxicity and binding of misonidazole by low glucose concentration.
abstract: The modulation of the hypoxic toxicity and binding of Misonidazole (MISO) by glucose and lactate was studied by exposing exponential EMT6/Ro cells to 5 mM MISO under hypoxic conditions. The concentrations of glucose used were 0.015 mM and 5 mM, and the concentrations of lactate were 0, 3 and 10 mM. There was no significant hypoxic toxicity due to MISO in the absence of glucose. However, with 5 mM glucose, after a latent period of 0.5 hours, there was a rapid decrease in cell survival to less than 0.1% at 2.5 hours incubation in 5 mM MISO. The binding of MISO was also increased by glucose. The amount of MISO bound to cells in 0.015 mM glucose leveled off at 2 nmoles MISO/7 X 10(5) cells at 1 hour, whereas the binding in 5 mM glucose continued to increase to more than 5 nmoles MISO/7 X 10(5) cells after 3 hours incubation. There was no detectable effect of lactate on the binding of MISO to the cells either in 0.015 mM or 5 mM glucose. The high affinity of this binding was indicated by the lack of exchange of radioactive MISO with non-radioactive MISO even after 2 hours of incubation. These data showed that glucose concentrations could modify the toxicity and binding of MISO to hypoxic cells.
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D051379:Mice; D008920:Misonidazole / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000502:physiology*
chemical_list: D007773:Lactates; D019344:Lactic Acid; D008920:Misonidazole; D005947:Glucose; D010100:Oxygen