Optimization of tumour radiotherapy: Part V--Radiosensitization by 2-deoxy-D-glucose and DNA ligand Hoechst-33342 in a murine tumour.

ABSTRACT

Radiosensitizing effects of combination of a minor groove DNA ligand, Hoechst-33342, with the glucose analogue and inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG) have been investigated in Ehrlich ascites tumour (EAT) bearing mice following focal irradiation of the tumour with 60Co gamma-rays. Treatment-induced tumour growth delay and tumour free animal survival were evaluated as parameters of radiation response. Focal irradiation of the tumour with a single fraction of 10 Gy induced a moderate delay in tumour growth but did not lead to complete regression in any of the tumours. Intravenous administration of H-342 1 hr before irradiation enhanced radiation-induced growth delay in a dose dependent manner. Complete regression of the tumour was observed only at a dose of 10 mg/kg body wt, leading to a cure (tumour free survival for more than 100 days) rate of 55%. Administration of 2-DG (2 g/kg body wt; i.v.), immediately before irradiation significantly enhanced radiation-induced growth delay and resulted in a cure rate of 45%. In combination with this dose of 2-DG (2 g/kg body wt), H-342 at a lower dose (5 mg/kg body wt) significantly enhanced the cure rate to 66%. H-342 or 2-DG given alone or in combination at the doses investigated here did not show any significant effects on the unirradiated tumour.