CHARACTERIZATION OF AN OXIDATION-RESISTANT TUMOR-CELL LINE AND ITS SENSITIVITY TO IMMUNE-RESPONSE AND CHEMOTHERAPY

被引:6
作者
SAURI, H [1 ]
KIM, AT [1 ]
SHAU, HY [1 ]
机构
[1] UNIV CALIF LOS ANGELES, SCH MED, JONSSON COMPREHENS CANC CTR, LOS ANGELES, CA 90024 USA
关键词
D O I
10.1006/jsre.1995.1083
中图分类号
R61 [外科手术学];
学科分类号
摘要
Aerobic cells have several scavenger systems for protection from reactive oxygen species (ROS). We developed an ROS-resistant variant of the human erythroleukemic cell line K562 by culturing cells in glucose oxidase to produce hydrogen peroxide. Testing the activity of the scavenger systems for ROS showed these cells had a 25- to 28-fold increase in catalase activity. We therefore termed this variant cell line K562-CAT. There was no similar increase in glutathione content or activity of superoxide dismutase and glutathione peroxidase. To determine what effect the increased catalase activity would have on the immune response to these tumor cells, we compared K562 and K562-CAT sensitivity to tumor necrosis factor-alpha (TNF alpha) activated polymorphonuclear neutrophil (PMN), natural killer (NK), and lymphokine-activated killer (LAK) cells. K562-CAT showed a significant increase in resistance to TNF alpha-activated PMN but not to NK or LAK, confirming the role of ROS in the former but not the latter. We also tested K562-CAT sensitivity to cisplatin and mitomycin C, agents known to involve ROS in their cytotoxic mechanism. There was no increased resistance in K562-CAT compared to parental K562, indicating that catalase is not involved in tumor cell resistance to those drugs. Given the characteristics of its resistance to the immune response, K562-CAT or a similar catalase-hyperexpressing cell line could be useful in determining the significance of TNF alpha-activated PMN in antitumor defenses. (C) 1995 Academic Press, Inc.
引用
收藏
页码:526 / 535
页数:10
相关论文
共 60 条
[1]  
Geiger P.G., Thomas J.P., Girotti A.W., Lethal damage to L1210 cells by exogenous lipid hydroperoxides: Protective role of glutathione-dependent selenoperoxidases, Arch. Biochem. Bio-Phys, 288, (1991)
[2]  
Lin F., Thomas J.P., Girotti A.W., Hyperexpression of catalase in selenium-deprived murine L1210 cells, Arch. Biochem. Biophys, 305, (1993)
[3]  
Park Y.K., Erson R.L., Spitz D.R., Hahn G.M., Hypoxia and resistance to hydrogen peroxide confer resistance to tumor necrosis factor, in murine L929 cells, Radiat. Res, 131, (1992)
[4]  
Spitz D.R., Adams D.T., Sherman C.M., Roberts R.J., Mechanisms of cellular resistance to hydrogen peroxide, hyper-oxia, and 4-hydroxy-2-nonenal toxicity: The significance of increased catalase activity in H2Oz-resistant fibroblasts, Arch. Biochem. Biophys, 292, (1992)
[5]  
Shau H., Gupta R.K., Golub S.H., Identification of a natural killer enhancing factor from human erythroid cells, Cell Immunol, 147, (1993)
[6]  
Shau H., Butterfield L.H., Chiu R., Kim A., Cloning and sequence analysis of candidate human natural killer-enhancing factor genes, Immunogenetics, 40, (1994)
[7]  
Shau H., Kim A., Identification of natural killer enhancing factor as a major antioxidant in human red blood cells, Biochem. Biophys. Res. Commun, 199, (1994)
[8]  
Asher A., Mule J.J., Reichert C.M., Shiloni E., Rosenberg S.A., Studies on the antitumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo, J. Immunol, 138, (1987)
[9]  
Havel E.A., Fiers W., North R.J., The antitumor function of tumor necrosis factor (TNF). I. Therapeutic action of TNF against established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity, J. Exp. Med, 167, (1988)
[10]  
Palladino M.A., Shalaby M.R., Kramer S.M., Ferraiolo R.L., Baughman R.A., Deleo A.B., Crase D., Marafino B., Aggarwal B.B., Figari I.S., Liggit D., Patton J.S., Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: Induction of tumor specific immunity, J. Immunol, 138, (1987)