Cytotoxic effect of tumour necrosis factor -alpha on sarcoma F cells at tumour relevant oxygen tensions

We have investigated the response of a murine tumour cell line, the sarcoma F (SaF), to tumour necrosis factor-alpha (TNF) at oxygen tensions known to occur in vivo. Using the Eppendorf pO2 histograph, the oxygen status of SaF tumours grown in situ was assessed. The median pO2 of the SaF is less than 1% oxygen with over 90% of values at or below 15 mmHg (< 2% O2). SaF cells primed in vitro for 24 h at tumour relevant oxygen tensions required at least four times more TNF to reduce cell number to 50% of controls following a 24 h incubation period in 21% oxygen. Chronic exposure of SaF cells to hypoxia during several passages increased resistance to TNF more than 60-fold. The oxygen sensitizing effect is transient as the resistance of hypoxic cells to TNF was reversed after 24 h incubation in air. These data clearly show that oxygen tension is a key modulator of the cytotoxic action of this important cytokine.