Differential analysis of closely related Nb2-lymphoma cell lines can be used for identification of changes in biochemical properties associated with the malignant progression of certain T-cell cancers. As tumors progress, they tend to show metabolic alterations such as an increased resistance to oxidative stress, a characteristic that may be correlated with changes in intrinsic antioxidant levels (e.g., glutathione) and in activities of associated enzymes such as the glutathione redox pathway. Whether increases in malignancy of Nb2 cells were associated with changes in cellular glutathione levels and activities of glutathione-metabolizing enzymes was addressed. To evaluate this relationship, 3 cell lines, showing increased malignancy, were used: Nb2-U17 (hormone-dependent, non-metastatic), Nb2-11 (hormone-dependent, metastatic), Nb2-SFJCD1 (growth factor-independent, metastatic). Compared to Nb2-U17 and Nb2-11 cells, the highly progressed Nb2-SFJCD1 lymphoma cells maintain low basal glutathione levels. However, the Nb2-SFJCD1 cells display an enhanced capacity to produce glutathione when challenged with an oxidative stress and show a significantly higher resistance to H2O2-induced apoptosis.