Ascorbic acid recycling in Nb2 lymphoma cells: Implications for tumor progression

Analysis of cultured rat "Nb2 lymphoma" cell lines, showing different degre es of malignant progression, can lead to identification of phenotypic chang es associated with this phenomenon in T-cell cancers. In the present study we have compared the metastatic sublines, Nb2-11 and Nb2-SFJCD1, with regar d to ascorbate and glutathione recycling, important processes in cellular p rotection from oxidative stresses. Whereas the Nb2-11 subline is prolactin (PRL)dependent, the genetically related Nb2-SFJCD1 subline is growth factor -independent and shows more chromosomal alterations, indicative of more adv anced progression. The Nb2-SFJCD1 cells, compared to the Nb2-11 cells, were less sensitive to toxic effects of dehydroascorbate, a potentially toxic o xidation product of ascorbate. Results were consistent with a significantly higher production of reducing equivalents (e.g., NADPH, GSH) and an accele rated reduction of dehydroascorbate by homogenates of Nb2-SFJCD1 cells. How ever, the increased resistance was apparently not directly related to the c ellular uptake and reduction of dehydroascorbate by whole cells, which was similar in both cell Lines. Observations indicate that Nb2 lymphoma cells, in their progression to malignancy, can acquire an enhanced capability to p rotect themselves from oxidative damage assisting them in withstanding the oxidative stress that anti-neoplastic drags can cause. The adaptation may a lso be a mechanism that is utilized by tumor cells in suppressing apoptosis and other protective cellular functions facilitating, or potentiating, a t umor cell's ability to become more metastatic. However, the mechanism leadi ng to this augmented capacity of Nb2 lymphoma cells to resist oxidative str ess in not known and is the subject for further study. (C) 1998 Elsevier Sc ience Inc.