Radiobiological hypoxia of a transplanted rat tumour and the effect of treatment with cyclophosphamide

Abstract

Isologous tumours, 8–10 mm in diameter, of the 37th–40th generation spontaneous adenocarcinoma LMC I have been grown subcutaneously in 150–200 g female Wistar rats and irradiated with 60Co γ-rays before or 1, 4, 7 or 10 days after intraperitoneal injection of 150 mg/kg of cyclophosphamide (CP). Dose-response curves for delay in growth of the tumour given aerobic or hyperbaric (HBO) irradiation alone were biphasic and, above 15 Gy (AIR) and 20 Gy (HBO), their response was governed by a component of hypoxic cells. One day after CP the response of the tumour to aerobic irradiation was the same as when rendered hypoxic by clamping 15 min prior to treatment indicating that only hypoxic tumour cells survive in animals treated with drug. Three days later hypoxia is reduced by reoxygenation, but the hypoxic fraction is still significantly higher than before treatment with CP. Only by 7 and 10 days had the hypoxic fraction of clonogenic cells been reduced to a level characteristic of the untreated tumour. Even though at 4 days after giving drug the hypoxic component of cells was significantly larger than normal for rats breathing air, no resistant component was found in the tumour response for HBO irradiation. This suggests that processes leading to the reoxygenation of a tumour after an initial treatment with drug may themselves permit an enhanced effect of subsequent HBO irradiation.