Influence of clamping-induced ischemia and reperfusion on the response of a mouse melanoma to radiation and hyperthermia

Purpose: To study the response of a mouse melanoma to radiation and hyperthermia under acute hypoxia and reperfusion. Materials and methods: B16F1 melanoma of 100 ± 10mm³, in C57BL mouse, were locally exposed to 10 Gy gamma radiation (RT), 43°C for 30 min (HT) in a water bath, or RT followed immediately by HT, under clamping (acute hypoxia) or 1 h after reperfusion. Tumour regression, volume doubling time (VDT), growth delay (GD), apoptosis and microvascular density (MVD) were studied. Results: Under clamping, HT increased the VDT and GD to > 20 days above control and resulted in > 50% regression (PR) in all the tumours, whilst RT + HT synergistically enhanced VDT and GD. Under reperfusion, HT produced 25% PR against 16% by RT, with no increase in VDT and GD compared to RT. RT + HT significantly enhanced VDT and GD above that of RT or HT, but did not further increase PR of reperfused tumours. HT under clamping caused > 50% increase in apoptic cells over control and decreased MVD to 1/3rd of control. RT + HT further enhanced apoptotic cells to > 70% and reduced MVD to 1/6th of control. Conclusions: These results suggest that combination of radiotherapy with hyperthermia could benefit treatment of tumours with ischemia-induced acute hypoxia.