Optimization of tumour radiotherapy: Part V--Radiosensitization by 2-deoxy-D-glucose and DNA ligand Hoechst-33342 in a murine tumour.
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.
Dwarakanath
B S
BS
Department of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi.
Singh
S
S
Jain
V
V
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D001562:Benzimidazoles; D004273:DNA, Neoplasm; D008024:Ligands; D011838:Radiation-Sensitizing Agents; D003847:Deoxyglucose; C017807:bisbenzimide ethoxide trihydrochloride