title: Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker.
abstract: We characterized the oxidative stress (OS) status by the levels of reduced/oxidized glutathione (GSH/GSSG), malondialdehyde (MDA) and the mutagenic base 8-oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) in human gastric carcinoma (HGC) samples and compared the results with normal tissue from the same patients. We also analyzed 8-oxo-dG in peripheral mononuclear cells (PMNC) and urine from healthy control subjects and in affected patients in the basal state and one, three, six, nine and twelve months after tumor resection. The levels of DNA repair enzyme mRNA expression (hOGG1, RAD51, MUYTH and MTH1) were determined in tumor specimens and compared with normal mucosa. Tumor specimens exhibited increased levels of MDA and 8-oxo-dG compared with normal gastric tissue. GSH levels were also increased, while GSSG levels remained stable. DNA repair enzyme mRNA expression was induced in the tumor tissues. Levels of 8-oxo-dG were significantly elevated in both urine and PMNC of gastric cancer patients compared with healthy controls. After gastrectomy, the levels of the damaged base in urine and PMNC decreased progressively to values close to those found in the healthy population. The high levels of 8-oxo-dG in urine may be related to the increased induction of DNA repair activity in tumor tissue, and the changes observed after tumor resection support its potential use as a tumor marker.
authors: Clinical Analysis Service, CDB-General University Hospital, Avda. Tres Cruces s/n., Valencia 46014, Spain. guillermo.saez@uv.es.
authors: Silvia
authors: S
authors: Borrego
authors: Antonio
authors: A
authors: Vazquez
authors: Francisco
authors: F
authors: Dasí
authors: Concha
authors: C
authors: Cerdá
authors: Antonio
authors: A
authors: Iradi
authors: Carmen
authors: C
authors: Tormos
authors: Julia M
authors: JM
authors: Sánchez
authors: Leticia
authors: L
authors: Bagán
authors: Javier
authors: J
authors: Boix
authors: Cristóbal
authors: C
authors: Zaragoza
authors: Jordi
authors: J
authors: Camps
authors: Guillermo
authors: G
authors: Sáez
references: J Toxicol Environ Health A. 2007 Jun;70(11):956-63
references: 17479411
references: Free Radic Biol Med. 2001 Jun 1;30(11):1286-92
references: 11368926
references: Mutat Res. 2005 Jul 1;574(1-2):58-66
references: 15914207
references: Mol Carcinog. 1997 Apr;18(4):232-43
references: 9142218
references: Acta Biochim Pol. 2003;50(2):549-53
references: 12833180
references: FASEB J. 2010 Apr;24(4):1249-60
references: 19966135
references: J Mol Med (Berl). 1996 Jun;74(6):297-312
references: 8862511
references: Oncogene. 1994 Aug;9(8):2277-81
references: 8036011
references: Free Radic Biol Med. 1999 Sep;27(5-6):647-66
references: 10490286
references: Nature. 2000 Feb 24;403(6772):859-66
references: 10706276
references: Mutat Res. 1999 Apr 26;441(1):11-9
references: 10224318
references: Anal Biochem. 2000 Dec 1;287(1):65-72
references: 11078584
references: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11021-5
references: 1332067
references: Nutr Metab Cardiovasc Dis. 2002 Oct;12(5):259-66
references: 12616805
references: Oncogene. 2002 Dec 16;21(58):8905-25
references: 12483508
references: Cancer Lett. 2005 Sep 28;227(2):133-9
references: 16112416
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references: 19474385
references: J Nutr. 2004 Nov;134(11):3188S-3189S
references: 15514301
references: Clin Cancer Res. 2010 Nov 1;16(21):5211-21
references: 20705614
references: Anticancer Res. 2002 Jul-Aug;22(4):2311-6
references: 12174919
references: Cancer Lett. 2012 Apr 28;317(2):144-9
references: 22115963
references: Am J Hematol. 1994 Nov;47(3):237-8
references: 7942792
references: Proc Natl Acad Sci U S A. 1984 Nov;81(22):6943-7
references: 6594673
references: Cancer Lett. 2005 Mar 10;219(2):125-35
references: 15723711
references: Cancer Res. 2003 Aug 15;63(16):4899-902
references: 12941813
references: Free Radic Biol Med. 1997;22(7):1203-9
references: 9098094
references: Nucleic Acids Res. 2002 Jan 15;30(2):E7
references: 11788733
references: J Natl Cancer Inst. 2005 Mar 2;97(5):384-95
references: 15741575
references: Scand J Clin Lab Invest Suppl. 1968;97:77-89
references: 4179068
references: Histopathology. 2009 Dec;55(6):696-704
references: 20002770
references: Cancer Lett. 2006 Feb 20;233(1):28-35
references: 15899547
references: Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-75
references: 17628657
references: J Biol Chem. 1987 Nov 5;262(31):15048-53
references: 3667623
references: Biochemistry. 1995 Jan 10;34(1):89-95
references: 7819228
references: Mol Carcinog. 1994 Nov;11(3):170-5
references: 7945806
references: Nature. 2008 Jul 24;454(7203):436-44
references: 18650914
references: Clin Cancer Res. 2000 Apr;6(4):1394-400
references: 10778969
references: Nucleic Acids Res. 1998 Apr 15;26(8):2001-7
references: 9518496
references: Cancer. 2010 Dec 15;116(24):5592-8
references: 20737569
references: Anal Biochem. 2004 Nov 15;334(2):239-50
references: 15494130
references: Nucleic Acids Res. 2000 Mar 15;28(6):1355-64
references: 10684930
references: Biochem Pharmacol. 1983 Sep 1;32(17):2529-34
references: 6615548
references: Free Radic Res. 2002 Mar;36(3):239-45
references: 12071341
references: Mutat Res. 2007 Jul 10;631(1):62-8
references: 17512776
references: Clin Chim Acta. 1973 May 18;45(3):281-5
references: 4513517
references: Mutat Res. 2004 Sep;567(1):1-61
references: 15341901
references: Carcinogenesis. 1990 Sep;11(9):1447-50
references: 2205403
references: Free Radic Biol Med. 2002 Oct 1;33(7):875-85
references: 12361799
references: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17992-7
references: 20855610
references: Free Radic Biol Med. 1990;8(6):583-99
references: 2193855
references: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Apr;27(2):120-39
references: 19412858
references: Nature. 1991 Jan 31;349(6308):431-4
references: 1992344
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Free Radic Biol Med. 2011 Jan 15;50(2):254-61
references: 21075202
references: Free Radic Biol Med. 1995 Apr;18(4):801-6
references: 7750803
references: J Clin Biochem Nutr. 2009 Nov;45(3):255-70
references: 19902015
references: Nature. 2001 May 17;411(6835):366-74
references: 11357144
references: Free Radic Biol Med. 2010 Dec 1;49(11):1603-16
references: 20840865
references: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):3-14
references: 18199707
references: Eur J Surg Oncol. 2007 Dec;33(10):1164-8
references: 17467227
references: Free Radic Res. 2007 May;41(5):546-54
references: 17454137
references: FEBS Lett. 1995 Jan 16;358(1):1-3
references: 7821417
references: Mutat Res. 2006 Oct 10;601(1-2):83-91
references: 16843501
references: Free Radic Biol Med. 2003 Jun 1;34(11):1447-57
references: 12757855
references: Mutat Res. 2011 Jun 3;711(1-2):193-201
references: 21216256
references: Cancer Res. 1994 Apr 1;54(7 Suppl):1918s-1923s
references: 8137312
references: Cancer Res. 1991 Feb 1;51(3):794-8
references: 1846317
references: Free Radic Biol Med. 1995 Apr;18(4):747-55
references: 7750799
references: Cancer Res. 1992 Apr 15;52(8):2298-303
references: 1559232
references: Cancer Lett. 2008 Jul 18;266(1):60-72
references: 18374480
references: Hepatogastroenterology. 2012 May;59(115):671-5
references: 22469707
references: Cancers (Basel). 2011 Sep 28;3(4):3740-61
references: 24213109
references: Int J Mol Sci. 2012;13(6):6711-29
references: 22837659
references: Int J Cancer. 1996 Feb 8;65(4):437-41
references: 8621223
references: Nature. 1987 May 7-13;327(6117):77-9
references: 3574469
references: FASEB J. 2003 Jul;17(10):1195-214
references: 12832285