Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.
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.
Miranda-Vilela
Ana L
AL
Departamento de Genética e Morfologia, Laboratório de Genética, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília/DF, Brasil. mirandavilela@unb.br
Alves
Penha Cz
PC
Akimoto
Arthur K
AK
Lordelo
Graciana S
GS
Gonçalves
Carlos A
CA
Grisolia
Cesar K
CK
Klautau-Guimarães
Maria N
MN
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
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
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