Relationship between energy status, hypoxic cell fraction, and hyperthermic sensitivity in a murine fibrosarcoma

The energy status, radiobiological hypoxic cell fraction, and hyperthermic sensitivity of a spontaneous murine fibrosarcoma, FSa-II, have been evaluated as a function of tumor size. Tumors were evaluated over the size range of 70 to 800 mm3. The concentration of the high-energy phosphate reservoir creatine phosphate progressively decreased by a factor of 5 with increasing tumor volume, and was matched by an increase in creatine. The concentration of ATP also decreased with increasing tumor size, although this decrease was substantially less pronounced. The sum of ATP, ADP, and AMP did not vary with tumor size, suggesting that the necrotic fraction remained constant. The decrease in energy status occurred in parallel with an increase in the size of the hypoxic cell fraction and with increasing thermal sensitivity. The results suggest that energy status may be an important modifier of hyperthermic sensitivity in vivo and reflect tissue oxygen concentration.