CHANGES IN GLUTATHIONE REDOX CYCLING AND OXIDATIVE STRESS-RESPONSE INTHE MALIGNANT PROGRESSION OF NB2 LYMPHOMA-CELLS

Differential analysis of closely related Nb2-lymphoma cell lines can b e used for identification of changes in biochemical properties associa ted with the malignant progression of certain T-cell cancers. As tumor s progress, they tend to show metabolic alterations such as an increas ed resistance to oxidative stress, a characteristic that may be correl ated 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 glutathi one-metabolizing enzymes was addressed. To evaluate this relationship, 3 cell lines, showing increased malignancy, were used: Nb2-U17 (hormo ne-dependent, non-metastatic), Nb2-11 (hormone-dependent, metastatic), Nb2-SFJCDI (growth factor-independent, metastatic). Compared to Nb2-U 17 and Nb2-11 cells, the highly progressed Nb2-SFJCDI lymphoma cells m aintain low basal glutathione levels. However, the Nb2-SFJCDI cells di splay an enhanced capacity to produce glutathione when challenged with an oxidative stress and show a significantly higher resistance to H2O 2-induced apoptosis. (C) 1998 Wiley-Liss, Inc.