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Effects of Antioxidants on the Gamma-Radiation Damage of the Cultured Vascular Smooth Mucle Cells of Rat Aorta  

Lee, Jong-Doo (Department of Radiation Oncology, Yonsei University College of Medicine)
Choi, Hyoung-Chul (Departments of Pharmacology, College of Medicine, Yeungnam University)
Kang, Young-Jin (Departments of Pharmacology, College of Medicine, Yeungnam University)
Kim, Myung-Se (Departments of Radiation Oncology, College of Medicine, Yeungnam University)
Lee, Kwang-Youn (Departments of Pharmacology, College of Medicine, Yeungnam University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.11, no.5, 2007 , pp. 189-195 More about this Journal
Abstract
To study the protective effects of antioxidants on the radiation damages of the cells, vascular smooth muscle cells(VSMC) from thoracic aorta of Sprague-Dawley rats were cultured and irradiated with gamma-ray. Cell viability was measured by direct cell counting and MTT assay, and flow cytometry was performed to measure fractional distributions of the cells. Gamma-ray irradiation inhibited cell proliferations accompanied with decreased G1 phase and increased S- and G2/M phases, and the maximum effects were observed at 1500 or 2000 cGy. Submaximal concentrations of antioxidants, such as allopurinol, vitamin C, N-acetylcycteine(NAC), lipoic acid, dihydrolipoic acid and rebamipide tended to increase the cell viability suppressed by low dose of radiation(500 cGy), and enalapril and vitamin E increased it significantly. Allopurinol, vitamin E, NAC, lipoic acid, captopril and enalapril significantly increased G1 phase. Allopurinol and vitamin E tended to increase c-Myc expression, detected by Western blot, that was reduced by the radiation, and enalapril increased it significantly. The cell viability and c-Myc expression were highly correlated(r=0.97) with each other. These results suggest that antioxidants, especially enalapril and vitamin E, recover the viability of VSMC from gamma-radiation injury, through a mechanism which includes increase of c-Myc protein expression.
Keywords
Antioxidant; Vascular smooth muscle cell; Proliferation; Cell cycle; Gamma ray; c-Myc;
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1 Benzie IF, Tomlinson B. Antioxidant power of angiotensin-converting enzyme inhibitors in vitro. Br J Clin Pharmacol 45:168-169, 1998   DOI   ScienceOn
2 Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19: 1-11, 1999   DOI   PUBMED
3 de Cavanagh EM, Fraga CG, Ferder L, Inserra F. Enalapril and captopril enhance antioxidant defenses in mouse tissues. Am J Physiol 272(2 Pt 2): R514-518, 1997
4 Fearon ER, Dang CV. Cancer genetics: tumor suppressor meets oncogene. Curr Biol 9: R62-65, 1999   DOI   ScienceOn
5 Greenstock CL. Radiation and aging: free radical damage, biological response and possible antioxidant intervention. Med Hypotheses 41: 473-82, 1993   DOI   PUBMED   ScienceOn
6 Hayon T, Dvilansky A, Shpilberg O, Nathan I. Appraisal of the MTT-based assay as a useful tool for predicting drug chemosensitivity in leukemia. Leuk Lymphoma 44: 1957-1962, 2003   DOI   ScienceOn
7 Hosseinimehr SJ, Mahmoudzadeh A, Akhlagpour S. Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation. Cell Biochem Funct 25: 389-394, 2007   DOI   ScienceOn
8 Kawano S, Sato N, Kamada T, Yamasaki K, Imaizumi T, Komemushi S. Protective effect of rebamipide (OPC-12759) on the gastric mucosa in rats and humans. Nippon Yakurigaku Zasshi 97: 371-380, 1991   DOI   PUBMED   ScienceOn
9 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63, 1983   DOI   PUBMED   ScienceOn
10 Rupnow BA, Murtha AD, Chen E, Knox SJ. Myc activation reduces fibroblast clonogenicity via an apoptotic mechanism that can be suppressed by a soluble paracrine factor. Cancer Lett 15; 127: 211-219, 1998
11 Thompson EB. The many roles of c-Myc in apoptosis. Annu Rev Physiol 60: 575-600, 1998   DOI   PUBMED   ScienceOn
12 Harapanhalli RS, Yaghmai V, Giuliani D, Howell RW, Rao DV. Antioxidant effects of vitamin C in mice following X-irradiation. Res Commun Mol Pathol Pharmacol 94: 271-287, 1996   PUBMED
13 Lehmann J, Pollet D, Peker S, Steinkraus V, Hoppe U. Kinetics of DNA strand breaks and protection by antioxidants in UVAor UVB-irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay. Mutat Res 407:97-108, 1998   DOI   PUBMED   ScienceOn
14 Antoku S, Aramaki R, Tanaka H, Kusumoto N. Protection of cultured mammalian cells by rebamipide. Fukuoka Igaku Zasshi 88: 247-252, 1997   PUBMED
15 Ramos FM, Pontual ML, de Almeida SM, Bóscolo FN, Tabchoury CP, Novaes PD. Evaluation of radioprotective effect of vitamin E in salivary dysfunction in irradiated rats. Arch Oral Biol 51: 96-101, 2006   DOI   ScienceOn
16 Anderson B, Khaper N, Dhalla AK, Singal PK. Anti-free radical mechanisms in captopril protection against reperfusion injury in isolated rat hearts. Can J Cardiol 12: 1099-1104, 1996   PUBMED
17 Zenk JL. New therapy for the prevention and prophylactic treatment of acute radiation syndrome. Expert Opin Investig Drugs 16: 767-770, 2007   DOI   PUBMED   ScienceOn
18 Breen AP, Murphy JA. Reactions of oxyl radicals with DNA. Free Radic Biol 18: 1033-1077, 1995   DOI   ScienceOn
19 Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 19: 227-250, 1995   DOI   ScienceOn
20 Faure M, Lissi EA, Videla LA. Antioxidant capacity of allopurinol in biological systems. Biochem Int 21: 357-366, 1990   PUBMED
21 Cotgreave I, Moldéus P, Schuppe I. The metabolism of N-acetylcysteine by human endothelial cells. Biochem Pharmacol 42: 13-16, 1991   DOI   ScienceOn
22 Tice RR, Strauss GH. The single cell gel electrophoresis/comet assay: a potential tool for detecting radiation-induced DNA damage in humans. Stem Cells 13 Suppl 1: 207-214, 1995   PUBMED
23 Scott BC, Aruoma OI, Evans PJ, O'Neill C, Van der Vliet A, Cross CE, Tritschler H, Halliwell B. Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free Radic Res 20: 119-133 1994   DOI   ScienceOn
24 Le Guen CA, Bain S, Barnett AH, Lunec J. Captopril inhibits the fluorescence development associated with glycation of proteins. Agents Actions 36: 264-270, 1992   PUBMED
25 Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11: 127-152, 2005   DOI   PUBMED   ScienceOn
26 Sakurai K, Sasabe H, Koga T, Konishi T. Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product. Free Radic Res 38: 487-494, 2004   DOI   ScienceOn
27 Maity A, McKenna WG, Muschel RJ. The molecular basis for cell cycle delays following ionizing radiation: a review. Radiother Oncol 31: 1-13, 1994   DOI   ScienceOn
28 Zimmerman K, Alt FW. Expression and function of myc family genes. Crit Rev Oncog 2: 75-95, 1990   PUBMED
29 Srivastava M, Chandra D, Kale RK. Modulation of radiation-induced changes in the xanthine oxidoreductase system in the livers of mice by its inhibitors. Radiat Res 157: 290-297, 2002   DOI   ScienceOn
30 Stewart MS, Cameron GS, Pence BC. Antioxidant nutrients protect against UVB-induced oxidative damage to DNA of mouse keratinocytes in culture. J Invest Dermatol 106: 1086-1089, 1996   DOI   ScienceOn
31 Yoshikawa T, Naito Y, Tanigawa T, Kondo M. Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance. Arzneimittelforschung 43: 363-366, 1993   PUBMED
32 Wan XS, Ware JH, Zhou Z, Donahue JJ, Guan J, Kennedy AR. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents. Int J Radiat Oncol Biol Phys 64: 1475-1481, 2006   DOI   PUBMED   ScienceOn
33 Aonuma H, Koide K, Masuda K, Watanabe I. Retinal light damage: protective effect of alpha-tocopherol. Jpn J Ophthalmol 41: 160-167, 1997   DOI   ScienceOn
34 Konopacka M, Widel M, Joanna Rzeszowska-Wolny. Modifying effect of vitamins C, E and beta-carotene against gamma-ray-induced DNA damage in mouse cells. Mutat Res 11: 417: 85-94, 1998
35 Kim M, Chung YH, Johnston RN. Reovirus and tumor oncolysis. J Microbiol 45: 187-192, 2007   과학기술학회마을
36 Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 6: 593-597, 1989   DOI   ScienceOn
37 Hayward WS, Neel BG, Astrin SM. Activation of a cellular oncogene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290: 475-480, 1981   DOI   ScienceOn
38 Liu J, Narasimhan P, Lee YS, Song YS, Endo H, Yu F, Chan PH. Mild hypoxia promotes survival and proliferation of SOD2- deficient astrocytes via c-Myc activation. J Neurosci 26 4329-4337, 2006   DOI   ScienceOn
39 Simko LC, Walker JH. Preoperative antioxidant and allopurinol therapy for reducing reperfusion-induced injury in patients undergoing cardiothoracic surgery. Crit Care Nurse 16: 69-73, 1996   PUBMED