Le. Sampson et Dj. Chaplin, THE INFLUENCE OF MICROENVIRONMENT ON THE CYTOTOXICITY OF TNF-PROPORTIONAL-TO IN-VITRO, International journal of radiation oncology, biology, physics, 29(3), 1994, pp. 467-471
Citations number
20
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Purpose: Investigations were undertaken to study the influence of oxyg
en levels on tumor necrosis factor proportional to (TNF proportional t
o) toxicity in vitro. Methods and Materials: The cell line used to ass
ess the cytotoxicity of TNF proportional to was the mouse fibroblast l
ine L929. The cell line was incubated under conditions of 21%, 10%, 5%
and 2% oxygen either before or during exposure to TNF proportional to
. All incubations with TNF were for 24 h in the presence of 1 mu g/ml
actinomycin D. Cell number was assessed immediately following treatmen
t by a colormetric method. Results: By preincubating L929 cells under
various oxygen conditions for 24 h prior to incubating with TNF propor
tional to, we show that pretreatment does influence TNF proportional t
o cytotoxicity since up to 50 times more TNF proportional to is requir
ed to elicit the same survival level when L929 cells have been preincu
bated for 24 h at oxygen levels relevant to those in solid tumors, tha
t is 2% rather than at 21%. A 24 h preincubation under an environment
of 5% oxygen is not as effective at inducing resistance to TNF proport
ional to as incubation under 2% oxygen. However, this resistance could
be significantly enhanced by lengthening the preincubation time. Inde
ed cells cultured for five passages under 5% oxygen levels are similar
to 50 times more resistant to TNF proportional to than cells cultured
under 21% oxygen. The resistance induced by conditions of reduced oxy
gen tension could be reversed over a 24 h period if cells were returne
d to an environment containing 21% oxygen. Conclusion: The oxygen cont
ent of the cellular microenvironment has a profound influence on the c
ytotoxic action of TNF.