Título:	Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay : a quasi-experimental study
Autor(es):	Miranda-Vilela, Ana Luisa Alves, Penha Cristina Zaidan Akimoto, Arthur K. Lordelo, Graciana S. Gonçalves, Carlos A. Grisólia, César Koppe Guimarães, Maria de Nazaré Klautau
Assunto:	Peróxido de hidrogênio DNA Mutagênese Células
Data de publicação:	5-Mai-2010
Editora:	BioMed Central
Referência:	VILELA, Ana Luisa Miranda et al. Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study. Environmental Health, v. 9, Article 21, 5 maio 2010. Disponível em: <https://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-9-21>. Acesso em: 20 jun. 2017. doi: https://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-9-21.
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 μM and 1 mM). Results: After 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. 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.
Licença:	© 2010 Miranda-Vilela et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI:	https://dx.doi.org/10.1186/1476-069X-9-21
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