2015, Number 2
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Rev Cub Gen 2015; 9 (2)
DNA damage and repair capacity in patients with von Hippel-Lindau
Gutierrez Gutierrez, Reinaldo; Pupo Balboa, Judith; Riverón Forment, Gretel; González Anta, Ana M; Pandolfi Blanco, Anamarys; de Armas Satiesteban, Aimara; Cásido Rodríguez, Mildrey; Rojas Betancourt, Iris
Language: Spanish
References: 15
Page: 36-39
PDF size: 433.81 Kb.
ABSTRACT
Von Hippel-Lindau disease is an autosomal dominant disorder which displays considerable inter- and intra-familial variability in phenotypic expression. VHL is characterized mainly by the development of tumors in various tissues and organs. Comet assay was used in this study to evaluate the basal levels of single stranded breaks in DNA, DNA repair capacity against oxidation induced by H2O2 and endogenous oxidized guanines damage in lymphocyte DNA of VHL patients compared to healthy subjects. No significant differences in DNA damage were observed between controls and patients (p › 0,05), but the DNA repair capacity was less efficient in VHL patients (p ‹ 0.05), and oxidative damage was increased. Using this assay we could identify poor repair capacity and increased oxidized guanine damage in VHL patients.
REFERENCES
Kaelin WG Jr. Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 2009; 115:2262- 72.
Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2:673-82;
Köhn L, Svenso U, Ljungberg B, Roos G. Specific genomic aberrations predict survival, but low mutation rate in cancer hot spots, in clear cell renal cell carcinoma. Appl Immunohistochem Mol Morphol 2015; 23(5): 334–342.
Yoshioka K, Atsumi Y, Nakagama H, Teraoka H. Development of cancer-initiating cells and immortalized cells with genomic instability. World J Stem Cells 2015; 26;7(2)
Collins AR. The Comet Assay for DNA Damage and Repair Principles, Applications, and Limitations Mol Biotechnol; 2004; 26(3):249-61.
Wang Y, Cheng J, Li D, Duan H, Yang H, Bin P et al. Modulation of DNA Repair Capacity by Ataxia Telangiectasia Mutated Gene Polymorphisms among Polycyclic Aromatic Hydrocarbons– Exposed Workers. Toxicological Sciences 2011; 124(1): 99-108
Smith CC, O’Donovan MR, Martin EA. hOGG1 recognizes oxidative damage using the comet assay with greater specificity than FPG or ENDOIII. Mutagenesis 2006;21(3):185-90
Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. The tumor suppressor protein VHL targets HIF for oxygen-dependant proteolysis. Nature 1999; 399:271-5
Baldewijns MM,Van Vlodrop IJ,Vermeulen PB, Soetekouw PM, Van Engeland M, De Bruine AP.VHL and HIF signaling in renal cel carcinogenesis. J Pathol 2010; 221:125–38
Semenza GL. VHL and p53: tumor suppressors team up to prevent cancer. Mol Cell 2006; 22:437-9
Metcalf JL, Bradshaw PS, Komosa M, Greer SN, Stephen Meyn M, Ohh M.K63-ubiquitylation of VHL by SOCS1 mediates DNA double-strand break repair. Oncogene; 2014 20;33(8):1055-65
Jae-Seok Roe, Hwa-Ryeon Kim, In-Young Hwang, Nam-Chul Ha, Seong-Tae Kim, Eun-Jung Cho & Hong-DukYoun. Phosphorylation of von Hippel-Lindau protein by checkpoint kinase 2 regulates p53 transactivation. Cell Cycle 2011; 10:22, 3920-3928.
Schults MA, Sanen K, Godschalk RW, Theys , van Schooten FJ, Chiu RK. Loss of VHL in RCC Reduces Repair and Alters Cellular Response to Benzo[a]pyrene. Oncol 2013; 3: 270.
Schults MA,Timmerman L,God- schalk RW, Theys J, Wouters BG, Van Schooten FJ, et al. Diminished carcinogen detoxification is a novel mechanism for hypoxia-inducible factor 1 mediated genetic instability. J Biol Chem 2010; 285:14558–64.
Yuan J, Narayanan L, Rockwell S, Glazer PM. Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH. Cancer Res 2000; 60:4372–6.