Abstract
Understanding the response of tumors to ionizing radiation might potentially lead to improvement in tumor control and patient morbidity. Since the antioxidant status is likely to be linked to radioresponse, its modulation needs to be examined. Therefore, Swiss albino male mice (7–8 weeks old) with Ehrlich solid tumors were irradiated with different doses of gamma rays (0–9 Gy) at a dose rate of 0.0153 Gy/s; and enzymes involved in antioxidant functions were determined in the tumors. Radiation effects in terms of oxidative damage, LDH, nitric oxide and DNA fragmentation were also examined.
In tumors, the specific activity of SOD was increased with dose but declined 6 Gy onwards. GST, DTD and GSH showed an almost progressive increase. These enhanced activities might have resulted from the increased protein expression. This possibility was supported by the Western Blot analysis for GST protein. These changes might be closely linked to the radiation-induced oxidative stress as reflected by the enhanced levels of peroxidative damage, DNA fragmentation, LDH activity and nitric oxide levels. These findings may have relevance to radiation therapy of cancer as the elevated antioxidant status of irradiated tumors is likely to limit the effectiveness of radiation dose and adversely affect the therapeutic gain.
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References
Grubbe EH: Priority in the therapeutic use of X-rays. Radiology 21: 156–162, 1933
West CM, Hendry JH: Intrinsic radiosensitivity as a predictor of patient response to radiotherapy. BJR Suppl 24 (suppl): 146–152, 1992
Toyokuni S, Okamoto K, Yodoi J, Hiai H: Persistent oxidative stress in cancer. FEBS Lett 358: 1–3, 1995
Dallner D: Studies on the structural and enzymic organization of the membrane elements of liver microsomes. Acta Pathol Microbiol Scand 166 (suppl): 1–94, 1963
Marklund S, Marklund G: Involvement of superoxide anion radical in autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469–474, 1974
Aebi H: Catalase in vitro. In: S.P. Colowick and N.O. Kaplan (eds). Methods in Enzymology. Academic Press, New York, 1984, pp 121–126
Ernster L, Danielson L, Ljunggren M: DT-diaphorase, I. Purification from soluble fraction of rat liver cytoplasm. Biochim Biophys Acta 58: 171–188, 1962
Habig WH, Pabst MJ, Jacoby WB: Glutathione-S-transferase: The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130–7139, 1974
Bergmeyer HU, Bernt E: Lactic dehydrogenase. Meth Enzym Anal 2: 574–579, 1974
Thornalley PJ: The glyoxalase system in health and disease. Mol Aspects Med 14: 287–371, 1993
Varshney R, Kale RK: Effects of calmodulin antagonists on radiationinduced lipid peroxidation in microsomes. Int J Radiat Biol 58: 533–543, 1990
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275, 1951
Moron MA, Dipierre IW, Mannervick B: Levels of glutathione, glutathione reductase and glutathione-S-tranferase activities in rat lung and liver. Biochim Biophys Acta 582: 67–78, 1979
Snel CA, Paug KS, Mulder GJ: Glutathione conjugation of bromosulphophthalein in relation to hepatic glutathione content in the rat in vivo and in the perfused rat liver. Hepatology 21: 1387–1394, 1995
Griess P: Bemerkungen zu der abhandlung der HH: Wesely und Benedikt ‘Uber einige Azoverbundungen’. Ber Deutch Chem Ges 12: 426–428, 1879
Omura T, Sato R: The carbon monoxide binding pigment of liver microsomes. J Biol Chem 239: 2370–2378, 1964
Sellins KS, Cohen JJ: Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J Immunol 139: 3199–3206, 1987
Burton K: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323, 1956
Bozzi A, Mavalli, I, Finazzi Agro A, Strom R, Wolf A, Modovi B, Rotilio T: Enzyme defense against reactive oxygen derivatives. II. Erythrocyte and tumor cells. Mol Cell Biochem 10: 11–16, 1976
Docampo R, Cruz FS, Boveris A, Muniz RPA, Esquivel DMS: β-lapachone enhancement of lipid peroxidation and superoxide anion and hydrogen peroxide formation by sarcoma 180 ascites tumor cells. Biochem Pharmacol 28: 723–728, 1979
Sun Y: Free radicals, antioxidant enzymes and carcinogenesis. Free Radic Biol Med 8: 583–599, 1990
Morichetti E, Cundari E, Carratore RD, Bronzetti G: Induction of cytochrome P-450 and catalase activity in Saccharomyces cerevisiae by UV and X-ray irradiation, possible role for cytochrome P-450 in cell protection against oxidative damage. Yeast 5: 141–148, 1989
O'Brien PJ, Rahimtula AD: The peroxidase function of cytochrome P-450 with possible implication for carcinogenesis. In: A. Gustafsson, J. Carlstedt-Duke, A. Mode, J. Rafter (eds). Biochemistry, Biophysics and Regulation of Cytochrome P450. Elsevier Biomedical Press, Amsterdam, 1980, pp 273–282
Kappeli O: Cytochrome P-450 of yeasts. Microbiol Rev 50: 44–258, 1986
Iyanagi T, Yamazaki I: One-electron-transfer reactions in biochemical systems: Difference in mechanisms of quinone reduction by the NADH dehydrogenases and NAD(P)H dehydrogenase (DT-Diaphorase). Biochim Biophys Acta 216: 282–294, 1970
Landi L, Fiorentini D, Galli MC, Segura-Afuilar J, Beyer RE: DT-diaphorase maintains the reduced state of ubiquinones in lipid vesicles thereby promoting their antioxidant function. Free Radic Biol Med 22: 329–335, 1997
Beyer EB, Aguilar JS, Bernardo SD, Cavazzoni M, Fato R, Fiorentini D, Galli MC, Setti M, Landi L, Lenaz G: The role of DT-diaphorase in the maintenance of the reduced antioxidant form of CoQ in membrane systems. Proc Natl Acad Sci USA 93: 2528–2532, 1996
Choudhary D, Chandra D, Kale RK: Influence of methylglyoxal on antioxidant enzymes and oxidative damage. Toxicol Lett 93: 141–152, 1997
Choudhary D, Chandra D, Lochab SP, Sarma A, Kale RK: Response of the glyoxalase system to low doses of mixed radiation. Physica Medica 15: 27–33, 1999
Dixon DP, Cummins, I, Cole DJ, Edwards R: Glutathione-mediated detoxification system in plants. Curr Opin Plant Biol 1: 256–258, 1998
Szent Gyorgi A: Protein radicals, regulation and cancer. Int J Quant Chem Quant Biol Symp 4: 179–184, 1977
Penninckx MJ, Jaspers CJ, Legrain MJ: The glutathione-dependent glyoxalase pathway in the yeast Saccharomyces cerevisiae. J Biol Chem 258: 6030–6036, 1983
Thornalley PJ: Glutathione dependent detoxification of á-oxoaldehydes by the glyoxalase system: Involvement in disease mechanisms and antiproliferative activity of glyoxalase I inhibitors. Chem Biol Interact 111-112: 137–151,1998
Revesz L, Edgren M, Nishidai T: Mechanism of inherent radioprotection in mammalian cells. In: T. Sugahara (ed). Modifications of Radiosensitivity in Cancer Treatment. Academic Press, New York, 1984, pp 13–29
Leyko W, Bartosz G: Membrane effects of ionizing radiation and hyperthermia. Int J Radiat Biol 49: 743–770, 1986
Ramakrishnan N, Kalinich JF, McClain DE: Radiation-induced apoptosis in lymphoid cells: Induction, prevention and molecular mechanisms. In: E.A. Bump, K. Malaker (eds). Radioprotectors: Chemical, Biological and Clinical Perspectives. CRC Press LLC, Florida, 1998, pp 253–273
Wills ED: Biochemical diagnosis. In: E.D. Wills (ed). Biochemical Basis of Medicine. Wright, Bristol, UK, 1985, pp 489–499
Chandra D, Kale RK: Influence of gamma rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs. Int J Radiat Biol 75: 335–349, 1999
Das RM: DNA-binding bibenzimidazoles as radioprotectors. In: E.A. Bump, K. Malaker (eds). Radioprotectors. Chemical Biological and Clinical Perspectives. CRC Press, London, 1998, pp 127–150
Srivastava M, Kale RK: Effect of radiation on the xanthine oxidoreductase system in the liver of mice. Radiat Res 152: 257–264, 1999
Srivastava M, Kale RK: Radiomodulation of xanthine oxidoreductase system in the liver of mice by phenylmethylsulphonyl fluoride and dithiothreitol. Radiat Res 154: 94–103, 2000
Sharma R, Kale RK: Effect of radiation on glyoxalase I and glyoxalase II activities in spleen and liver of mice. Int J Radiat Biol 63: 233–238, 1993
Hooper NI, Tisdale MJ, Thornalley PJ: Modification of the glyoxalase system in human HL60 promyelocytic leukemia cells during differentiation to neutrophils in vitro. Biochim Biophys Acta 966: 362–369, 1988
Sethi U, Basu A, Guha-Mukherjee S: Control of cell proliferation and differentiation by regulating polyamine biosynthesis in cultures of Brassica and its correlation with glyoxalase I activity. Plant Sci 56: 167–175, 1988
Sutrave P, Rao AR: Studies in glyoxalase I in regenerating mouse spleen. Life Sci Adv 1: 141–145, 1982
Sharma-Luthra R, Kale RK: Inhibition of radiation induced changes in glyoxalase I activity in spleen and liver by phenothiazines. Int J Radiat Biol 67: 403–410, 1995
Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288: 487, 1991
Kerwin J, Lancaster J, Feldman P: Nitric oxide: A new paradigm for second messengers. J Med Chem 88: 4343–4361, 1995
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Agrawal, A., Choudhary, D., Upreti, M. et al. Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice. Mol Cell Biochem 223, 71–80 (2001). https://doi.org/10.1023/A:1017900810837
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DOI: https://doi.org/10.1023/A:1017900810837