Altered glutathione anti-oxidant metabolism during tumor progression in human renal-cell carcinoma

It has been proposed that oxidative stress develops in tumors, with importa nt consequences for growth and progression. To investigate this hypothesis, we measured low m.w. thiols, disulfides, protein-mixed disulfides and a po ol of major anti-oxidant enzymes in renal-cortex as well as renal-cell carc inoma (RCC) specimens at stages I-II and ill. Our data showed (i) a signifi cant increase in the levels of total intracellular glutathione at both tumo r stages (levels were 2.6-2.8 fold higher than those in the normal renal co rtex), (ii) a marked lowering of the GSH/GSSG ratio in stage I-II accompani ed by a significant decrease of many GSH-dependent enzymes (i.e., GPX, CST, GGT, GR) and (iii) unchanged GSH/GSSG ratio and GSH-dependent enzyme activ ity in stage III with respect to normal renal cortex. These results indicat e that relevant variations exist in the glutathione antioxidant system in t he different stages of RCC and support the hypothesis that oxidative stress plays an important role in RCC growth and progression. (C) 2001 Wiley-Liss , Inc.