Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo

The relationship among cancer growth, the glutathione redox cycle and the antioxidant system was studied in blood and in tumour cells. During cancer growth, the glutathione redox status (GSH/GSSG) decreases in blood of Ehrlich ascites tumour-bearing mice. This effect is mainly due to an increase in GSSG levels. Two reasons may explain the increase in blood GSSG: (a) the increase in peroxide production by the tumour that, in addition to changes affecting the glutathione-related and the antioxidant enzyme activities, can lead to GSH oxidation within the red blood cells; and (b) an increase of GSSG release from different tissues into the blood. GSH and peroxide levels are higher in the tumour cells when they proliferate actively, however GSSG levels remain constant during tumour growth in mice. These changes associate with low levels of lipid peroxidation in plasma, blood and the tumour cells. The GSH/GSSG ratio in blood also decreases in patients bearing breast or colon cancers and, as it occurs in tumour-bearing mice, this change associates with higher GSSG levels, especially in advanced stages of cancer progression. Our results indicate that determination of glutathione status and oxidative stress-related parameters in blood may help to orientate cancer therapy in humans.