Effect of the manipulation of oxyhemoglobin status by BW12C on tumor thermosensitivity and on blood flow in tumor and normal tissues in mice.

The effect of 70 mgkg-1 BW12C 30 min before heating on the thermosensitivity of RIF-1 leg tumors was studied. This schedule is known to increase the hypoxic fraction by a factor of 5. Heating, using a combined radio-frequency and saline bath technique, was for 30 min at 43, 43.5, and 44 degrees C and response was assayed by clonogenic cell survival immediately and 24 hr after treatment. BW12C did not alter RIF-1 thermosensitivity. The effects of heat up to 44 degrees C on the oxygen saturation curves of normal and BW12C-modified blood were compared and P50s were shown to rise from 36 to 52 mm Hg and 6.5 to 8.0 mm Hg respectively, showing the latter to be relatively resistant to right-shifting by heat. 86Rb extraction studies on BW12C-treated unheated animals showed that blood flow in leg and flank tumours 60 min after BW12C was reduced to 64% and 34% of control values respectively, indicating a further mechanism for induction of tumour hypoxia by BW12C. Blood flow in leg muscle, liver, and spleen was unchanged but in kidney and lung was increased to 127% and 119% of control respectively 60 min after BW12C.