N. Matsubara et al., POSSIBLE INVOLVEMENT OF FREE-RADICAL SCAVENGING PROPERTIES IN THE ACTION OF TUMOR-NECROSIS-FACTOR-ALPHA, Free radical biology & medicine, 22(4), 1997, pp. 679-687
Constitutive production of hydroxyl radicals from four established can
cer cell lines was detected as spin adducts of 5,5-dimethyl-1-pyroline
-N-oxide (DMPO), using an electron spin resonance spectrometer. The ge
nerated hydroxyl radicals was decreased in three out of four cancer ce
ll lines when incubated in vitro for 3 h with TNF-alpha No direct scav
enging effect of TNF-alpha on hydroxyl radicals or superoxide anions w
as observed in the in vitro radical generation system. The modulation
of intracellular reactive oxygen species of these cancer cells by addi
ng menadione or CuDIPS to the culture medium changed the antiprolifera
tive effect of TNF-alpha on the cells. The ultrastructural localizatio
n of the radical-generating sites in cancer cells was visualized using
the diaminobenzidine/horseradish peroxide histochemical system at the
electron microscopic level. The hydrogen peroxide-dependent formation
of electron-dense materials localized at the mitochondrial membranes
was decreased after the treatment of the cancer cells with TNF-alpha.
These data indicate that the reduction of radical generation in cancer
cells by TNF-alpha may be an early mechanism that contributes to the
antiproliferative effect of this cytokine on some cancer cells. Copyri
ght (C) 1997 Elsevier Science Inc.