Em. Lynch et al., CYTOTOXIC EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA ON SARCOMA F-CELLS ATTUMOR RELEVANT OXYGEN-TENSIONS, Acta oncologica, 34(3), 1995, pp. 423-427
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.