Abstract
BackgroundNormal 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.MethodsWe 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 μM and 1 mM).ResultsAfter treatment with H2O2 at 250 μM, 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.ConclusionsThe 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.
Highlights
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
The CAT locus was appropriate for a heterozygote deficit (p = 0.0085), while the MnSOD locus was for a heterozygote excess (p < 0.001)
For GSTM1 and GSTT1, results were compatible with heterozygote deficit, due to homozygous (+/+, wild type) and heterozygous (+/-) being considered together within non-null genotypes, given that the PCR method is not suitable for distinguishing these genotypes
Summary
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. A certain level of damage cannot be avoided, oxidative stress can occur when the balance is upset, either by an excessive production of ROS, by deficient antioxidant defenses, or by a combination of both [5] In such circumstances, ROS may interact with cellular biomolecules, such as DNA, leading to modification and potentially serious consequences for the cell [8]. ROS may interact with cellular biomolecules, such as DNA, leading to modification and potentially serious consequences for the cell [8] In this context, the comet assay could be used to evaluate this damage, because it is widely accepted as a standard method for assessing DNA damage type in individual cells [5,9,10,11]. It is used to investigate DNA damage and repair in different cell types in response to a range of DNA-damaging agents, as well as monitoring the effects of dietary antioxidants [5,9,10,11]
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