The effect of prolonged high dose misonidazole on tumor response to radiation.

WHFIB and SA F tumors were exposed to misonidazole (MISO) concentrations of 2.5 mM or more for up to 4 hours (SA F) or 6 hours (WHFIB). There was no increase in the MISO enhancement ratio (SER) in the SA F for a 4 hour exposure to MISO relative to that following a single injection. In the WHFIB tumor, the ER increased from 2.2 for a single MISO injection to 2.5 for a 4 hour contact with MISO for tumor growth delay, and from 2.1 to 2.3 for a cloning assay. (These differences may not be statistically significant) Prolonged contact with MISO was toxic and reduced the body temperature by 4 to 5 degrees C. For WHFIB cells in vitro, when the contact time (in hypoxia) with 2.5 mM MISO was increased from 0.5 to 2.5 hours, the ER increased from 2.1 to 2.9 at 37 degrees C and from 1.9 to 2.5 at 33 degrees C.