title: Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.
abstract: BACKGROUND
  Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events.
  
  
  METHODS
  We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H2O2), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 microM and 1 mM).
  
  
  RESULTS
  After treatment with H2O2 at 250 microM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress.
  
  
  CONCLUSIONS
  The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.
authors.affiliation: Departamento de Genética e Morfologia, Laboratório de Genética, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília/DF, Brasil. mirandavilela@unb.br
authors.forename: Ana L
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.forename: Penha Cz
authors.initials: PC
authors.lastname: Alves
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Akimoto
authors.forename: Graciana S
authors.initials: GS
authors.lastname: Lordelo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonçalves
authors.forename: Cesar K
authors.initials: CK
authors.lastname: Grisolia
authors.forename: Maria N
authors.initials: MN
authors.lastname: Klautau-Guimarães
mesh_terms: D000293:Adolescent; D000328:Adult; D002374:Catalase / Q000235:genetics; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic / Q000187:drug effects* / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1
chemical_list: D006242:Haptoglobins; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D007703:Peptidyl-Dipeptidase A; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
references.citation: Am J Epidemiol. 2000 Jan 1;151(1):7-32
references.pmid: 10625170
references.citation: Cytometry A. 2007 Nov;71(11):905-14
references.pmid: 17879239
references.citation: Carcinogenesis. 2001 May;22(5):827-9
references.pmid: 11323405
references.citation: Mutagenesis. 1999 Sep;14(5):497-504
references.pmid: 10473654
references.citation: Hum Genet. 1997 Aug;100(2):163-6
references.pmid: 9254843
references.citation: Proc Soc Exp Biol Med. 1999 Dec;222(3):293-8
references.pmid: 10601888
references.citation: Nucleic Acids Res. 1992 Mar 25;20(6):1433
references.pmid: 1313972
references.citation: Mutagenesis. 2008 May;23(3):183-90
references.pmid: 18256034
references.citation: FASEB J. 2003 Jul;17(10):1195-214
references.pmid: 12832285
references.citation: Am J Hum Genet. 2000 Aug;67(2):444-61
references.pmid: 10873790
references.citation: Circulation. 2001 Sep 25;104(13):1571-4
references.pmid: 11571254
references.citation: BMC Med Genet. 2008 Apr 21;9:30
references.pmid: 18423055
references.citation: J Nutr. 2004 Nov;134(11):3173S-3174S
references.pmid: 15514293
references.citation: Toxicol Appl Pharmacol. 2007 Aug 15;223(1):46-55
references.pmid: 17631926
references.citation: Int J Lab Hematol. 2007 Apr;29(2):92-110
references.pmid: 17474882
references.citation: Arch Biochem Biophys. 2001 May 1;389(1):84-93
references.pmid: 11370676
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):146-9
references.pmid: 14744747
references.citation: Psychiatry Res. 2006 Feb 28;141(2):123-8
references.pmid: 16413612
references.citation: Thorax. 2006 May;61(5):394-9
references.pmid: 16467073
references.citation: Mutat Res. 1995 Jan;336(1):69-77
references.pmid: 7528897
references.citation: Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):281-2
references.pmid: 10669620
references.citation: Urology. 2005 Oct;66(4):769-74
references.pmid: 16230136
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9
references.pmid: 9012815
references.citation: Mutat Res. 1997 Dec;385(3):223-33
references.pmid: 9506891
references.citation: Biochem Biophys Res Commun. 1996 Sep 13;226(2):561-5
references.pmid: 8806673
references.citation: Toxicology. 2003 Jul 15;189(1-2):41-54
references.pmid: 12821281
references.citation: Mutat Res. 2009 Jan-Feb;681(1):24-32
references.pmid: 18054270
references.citation: Acta Med Okayama. 1998 Aug;52(4):173-81
references.pmid: 9781267
references.citation: Cancer Res. 2009 Oct 15;69(20):8183-90
references.pmid: 19826042
references.citation: Clin Chem. 1996 Oct;42(10):1589-600
references.pmid: 8855140
references.citation: Genet Mol Biol. 2010 Apr;33(2):359-67
references.pmid: 21637495
references.citation: Clin Chem Lab Med. 2006;44(5):542-7
references.pmid: 16681422
references.citation: Genet Mol Res. 2009;8(1):284-90
references.pmid: 19291877
references.citation: J Intern Med. 2001 May;249(5):451-9
references.pmid: 11350569
references.citation: Nat Genet. 2008 Mar;40(3):340-5
references.pmid: 18246066
references.citation: J Korean Med Sci. 2005 Dec;20(6):1089-92
references.pmid: 16361831
references.citation: Pharmacogenetics. 1996 Apr;6(2):187-91
references.pmid: 9156696
references.citation: J Appl Physiol (1985). 2007 Apr;102(4):1696-701
references.pmid: 17204574
references.citation: Exp Cell Res. 1988 Mar;175(1):184-91
references.pmid: 3345800
references.citation: Br J Nutr. 2006 Aug;96 Suppl 1:S34-7
references.pmid: 16923248
references.citation: Mutagenesis. 2008 May;23(3):191-205
references.pmid: 18326867
references.citation: Free Radic Res. 2010 Mar;44(3):322-31
references.pmid: 20109103
references.citation: Exp Gerontol. 2001 Feb;36(2):209-20
references.pmid: 11226737
references.citation: BMC Genet. 2006 Dec 11;7:56
references.pmid: 17156480
references.citation: Pharmacogenet Genomics. 2006 Apr;16(4):279-86
references.pmid: 16538174
references.citation: Cancer Res. 2003 Jun 15;63(12):3347-51
references.pmid: 12810669