Cytotoxic Effect of Tumour Necrosis Factor-Alpha on Sarcoma F Cells at Tumour Relevant Oxygen Tensions

Abstract

We have investigated the response of a murine tumour cell line, the sarcoma F (SaF), to tumour necrosis factor-α (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.