PMID: 3744943Jul 1, 1986Paper

Decreased hypoxic toxicity and binding of misonidazole by low glucose concentration

International Journal of Radiation Oncology, Biology, Physics
L L LingR M Sutherland

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.

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Citations

Oct 1, 1988·International Journal of Radiation Oncology, Biology, Physics·H de GrootR M Sutherland
Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·L HlatkyR K Sachs
Jan 1, 1989·International Journal of Radiation Oncology, Biology, Physics·L HlatkyR K Sachs
Jan 1, 1990·Critical Reviews in Oncology/hematology·C N Coleman, A T Turrisi

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