Enhancement of cytotoxicity of hydrogen peroxide by hyperthermia in Chinese hamster ovary cells: Role of antioxidant defenses

被引:38
作者
Lord-Fontaine, S [1 ]
Averill, DA [1 ]
机构
[1] Univ Quebec, Dept Chim & Biochim, Montreal, PQ H3C 3P8, Canada
关键词
hydrogen peroxide; antioxidant; glutathione; hyperthermia; oxidative stress; catalase; L-buthionine sulfoximine; aminotriazole; cytotoxicity; cell;
D O I
10.1006/abbi.1998.1087
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regional hyperthermia has potential for human cancer treatment, particularly in combination with systemic chemotherapy or radiotherapy. The mechanisms involved in heat-induced cell killing are currently unknown. Hyperthermia may increase oxidative stress in cells, and thus, oxidative stress could have a role in the mechanism of cell death. We use hydrogen peroxide as a model oxidant to improve understanding of interactions between heat and oxidative stress. Heat increased cytotoxicity of hydrogen peroxide in Chinese hamster ovary cells. Altered levels of cellular antioxidants should create an imbalance between prooxidant and antioxidant systems, thus modifying cytotoxic responses to heat and to oxidants, We determine the involvement of the two cellular antioxidant defenses against peroxides, catalase and the glutathione redox cycle, in cellular sensitivity to heat, to hydrogen peroxide, and to heat combined with the oxidant, Defense systems were either inhibited or increased. For inhibition studies, intracellular glutathione was diminished to less than 15% of its initial level by treatment with L-buthionine sulfoximine (1 mM, 24 h), Inhibition of catalase was achieved with 3-amino-1,2,4-triazole (20 mM, 2 h), which caused a 80% decrease in endogenous enzyme activity. To increase antioxidants, cells were pretreated with the thiol-containing reducing agents, N-acetyl-L-cysteine, 2-oxo-4-thiazolidine carboxylate, and 2-mercaptoethane sulfonate. These compounds increased intracellular glutathione levels by 30%. Catalase activity was increased by addition of exogenous enzyme to cells. We show that levels of glutathione and catalase affect cellular cytotoxic responses to heat and hydrogen peroxide, either used separately or in combination, These findings are relevant to mechanisms of cell killing at elevated temperatures and suggest the involvement of oxidative stress. (C) 1999 Academic Press.
引用
收藏
页码:283 / 295
页数:13
相关论文
共 64 条
[1]  
Ahmad S., 1995, OXIDATIVE STRESS ANT
[2]  
Anderson M E, 1997, Adv Pharmacol, V38, P65
[3]  
ANDERSON ME, 1989, HDB METHODS OXYGEN R, P317
[4]   ANTIOXIDANT DEFENSE-MECHANISMS OF ENDOTHELIAL-CELLS AND RENAL TUBULAR EPITHELIAL-CELLS INVITRO - ROLE OF THE GLUTATHIONE REDOX CYCLE AND CATALASE [J].
ANDREOLI, SP ;
MALLETT, C ;
MCATEER, JA ;
WILLIAMS, LV .
PEDIATRIC RESEARCH, 1992, 32 (03) :360-365
[5]  
BATES DA, 1986, CANCER RES, V46, P5477
[6]   THE ROLE OF THIOLS IN CELLULAR-RESPONSE TO RADIATION AND DRUGS [J].
BIAGLOW, JE ;
VARNES, ME ;
CLARK, EP ;
EPP, ER .
RADIATION RESEARCH, 1983, 95 (03) :437-455
[7]  
BISCHT KS, 1996, INDIAN J EXP BIOL, V34, P1183
[8]   SUPEROXIDE AND HYDROGEN-PEROXIDE IN RELATION TO MAMMALIAN-CELL PROLIFERATION [J].
BURDON, RH .
FREE RADICAL BIOLOGY AND MEDICINE, 1995, 18 (04) :775-794
[9]  
BURTON GM, 1979, INT J RADIAT ONCOL, V5, P878
[10]   PARTICIPATION OF REACTIVE OXYGEN SPECIES IN THE LYSOPHOSPHATIDIC ACID-STIMULATED MITOGEN-ACTIVATED PROTEIN-KINASE KINASE ACTIVATION PATHWAY [J].
CHEN, QL ;
OLASHAW, N ;
WU, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (48) :28499-28502