Department of Biochemistry, Kurukshetra University Kurukshetra, Haryana 136119, India.
Department of Biotechnology, Kurukshetra University Kurukshrtra, Haryana 136119, India.
Iran Biomed J. 2021 Jan;25(1):47-53. doi: 10.29252/ibj.25.1.47. Epub 2020 Aug 31.
Single nucleotide polymorphisms in 8-oxoguanine DNA glycosylase-1 (OGG1) gene modulates DNA repair capacity and functions as one of the first lines of protective mechanisms against 8-hydroxy-2'-deoxyguanosine (8-OHdG) mutagenicity. OGG1-Cys326 gene polymorphism may decrease DNA repair function, causing oxidative stress due to higher oxidative DNA damage. The main purpose of this study was to examine the link of oxidative and genotoxic DNA damage with DNA repair OGG1 gene polymorphism, in charcoal workers exposed to polyaromatic hydrocarbons.
Urinary 8-OHdG excretion (a biomarker of oxidative DNA damage) was determined in both exposed and control populations. Genotyping of OGG1 DNA repair gene in the blood samples of subjects was carried out by PCR-RFLP method.
The 8-OHdG urinary concentration was significantly higher (p < 0.05) in the exposed (geometric mean 12.33 ± 3.78) than in the unexposed (geometric mean 7.36 ± 2.29) population. DNA damage, as measured by 8-OHdG and tail moment content, was found to be significantly higher in OGG1 homozygous mutants (mt/mt; 18.81 ± 3.34; 6.04 ± 0.52) as compared to wild-type genotypes (wt/wt; 10.34 ± 2.25; 5.19 ± 2.50) and heterozygous (wt/mt) mutants (12.82 ± 2.81; 6.04 ± 0.93) in the exposed group.
We found a significant association of OGG1 heterozygous (wt/mt) and homozygous (mt/mt) variants with oxidative and genotoxic damage, suggesting that these polymorphisms may modulate the effects of polycyclic aromatic hydrocarbons exposure in occupational workers.
8-氧鸟嘌呤 DNA 糖基化酶-1（OGG1）基因中的单核苷酸多态性调节 DNA 修复能力，是对抗 8-羟基-2'-脱氧鸟苷（8-OHdG）致突变性的第一道保护机制之一。OGG1-Cys326 基因多态性可能会降低 DNA 修复功能，由于更高的氧化 DNA 损伤导致氧化应激。本研究的主要目的是检查氧化和遗传毒性 DNA 损伤与 DNA 修复 OGG1 基因多态性之间的联系，研究对象为暴露于多环芳烃的炭黑工人。
在暴露组和对照组中均测定尿 8-OHdG 排泄量（氧化 DNA 损伤的生物标志物）。通过 PCR-RFLP 法对受试者血液样本中的 OGG1 DNA 修复基因进行基因分型。
暴露组（几何均值 12.33 ± 3.78）中 8-OHdG 尿浓度明显高于未暴露组（几何均值 7.36 ± 2.29）（p < 0.05）。与野生型基因型（wt/wt；10.34 ± 2.25；5.19 ± 2.50）和杂合子（wt/mt）突变体（12.82 ± 2.81；6.04 ± 0.93）相比，OGG1 纯合突变体（mt/mt；18.81 ± 3.34；6.04 ± 0.52）的 DNA 损伤，如 8-OHdG 和尾巴矩含量所测量，明显更高。在暴露组中。
我们发现 OGG1 杂合子（wt/mt）和纯合子（mt/mt）变体与氧化和遗传毒性损伤显著相关，表明这些多态性可能调节职业工人多环芳烃暴露的影响。
