CYTOTOXIC EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA ON SARCOMA F-CELLS ATTUMOR RELEVANT OXYGEN-TENSIONS

We have investigated the response of a murine tumour cell line, the sa rcoma F (SaF), to tumour necrosis factor-alpha (TNF) at oxygen tension s known to occur in vivo. Using the Eppendorf pO(2) histograph, the ox ygen status of SaF tumours grown in situ was assessed. The median pO(2 ) of the SaF is less than 1% oxygen with over 90% of values at or belo w 15 mmHg (<2% O-2). SaF cells primed in vitro for 24 h at tumour rele vant oxygen tensions required at least four times more TNF to reduce c ell number to 50% of controls following a 24 h incubation period in 21 % oxygen. Chronic exposure of SaF cells to hypoxia during several pass ages increased resistance to TNF more than 60-fold. The oxygen sensiti zing effect is transient as the resistance of hypoxic cells to TNF was reversed after 24 h incubation in air. These data clearly show that o xygen tension is a key modulator of the cytotoxic action of this impor tant cytokine.