INHERENT CELLULAR DIFFERENCES MAY EXPLAIN THE DISSIMILAR SURVIVAL OF RIF-1 AND KHT TUMOR-CELLS UNDER AEROBIC AND HYPOXIC CONDITIONS

Although previous work has shown striking differences in radiobiologic al hypoxic fraction between KHT and RIF-1 murine sarcomas, intravascul ar oxyhaemoglobin (HbO(2) saturations have revealed less substantial v ariations. Using quantitative histological techniques, we have also fo und minor differences in the distributions of distances between tumour cells and the nearest bloods vessel for KHT versus RIF-1 sarcomas. We report here, the results of an investigation of the inherent ability of these tumour cells to withstand conditions of hypoxia by in vitro c ulturing under aerobic and anoxic conditions. Tumours were dissociated , seeded into culture dishes, and placed in air-tight aluminium chambe rs. These chambers were repeatedly evacuated and refilled with a mixtu re of 95% N-2 and 5% CO2 over a 2.5-h period. Following anoxic exposur e, cells were removed and replated, and the in vitro plating efficienc y (PE) was determined using a colony survival assay. After normalizing to aerobic controls, KHT tumour cells had a significantly lower PE, f ollowing a 16-hour exposure to anoxic conditions (0.4), than RIF-1 (0. 6). Increasing the hypoxic exposure to 4.0 h resulted in normalized PE s of 0.07 for KHT versus 0.4 for RIF-I, Although these results support the hypothesis that the two tumour lines have different inherent abil ities to withstand hypoxia, they do not explain the failure of direct measures of tumour oxygenation to correlate with the radiobiological h ypoxic fraction. Additional factors such as differences in oxygen diff usivity or oxygen consumption rates between tumour lines may also be i nvolved.