EFFECTS OF HYPOXIA ON THE CYTOTOXICITY MEDIATED BY TUMOR-NECROSIS-FACTOR-ALPHA

We investigated whether hypoxia (2% O-2, similar to 14 mm Hg partial p ressure) in comparison to O-2 atmospheric pressure (20.9% O-2, similar to 140 mm Hg) can affect the cytotoxic effects of tumor necrosis fact or-alpha (TNF) on the murine cell line L929. Under hypoxic conditions, L929 cells were significantly less inhibited by TNF treatment, even i n the presence of actinomycin D. Moreover, under hypoxic conditions, T NF cytotoxicity was significantly inhibited by glutathione, which has been shown to protect cells against oxidative damage induced by variou s agents. On the other hand, under aerobic conditions treatment with o ther antioxidant agents and active species oxygen scavengers, as super oxide dismutase and catalase, did not markedly affect the cytotoxicity of TNF. Since hypoxia occurs normally in most solid tumors, these res ults are interesting because they suggest a disadvantageous inhibition of the cytotoxic effects of TNF in vivo in hypoxic tissues and confir m that oxygen-dependent metabolic processes or free radicals are requi red to exert TNF-induced cytotoxicity.