Reduced DNA Glycosylases Expression and Oxidative DNA Damage Induced by Lead

Q4 Pharmacology, Toxicology and Pharmaceutics Toxicology International Pub Date : 2022-12-12 DOI:10.18311/ti/2022/v29i3/29322
Sirirak Hemmaphan, N. Bordeerat
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Abstract

Exposure to lead (Pb) continues to be a significant worldwide problem. Pb is a highly toxic heavy metal affecting several organ systems in the body. There has been reported to have potential genotoxic properties to various cells. However, the underlying mechanisms of lead-induced toxicity are still unknown. The present study aimed to investigate the lead-induced cytotoxicity in human renal proximal tubular epithelial cells and its underlying DNA damage mechanisms. Lead exposure caused DNA damage as demonstrated by increased 8-OHdG/dG ratio in cells even at a relatively normal dose (10μg/dL). Lead also led to producing oxidative stress as characterized by increased intensity of the Reactive Oxygen Species (ROS) indicator. ROS overproduction should be the reason for lead-induced DNA damage. Therefore, the effects of Lead on ROS elimination should be the main reason for lead-induced oxidative stress in human renal proximal tubular epithelial cells. After lead acetate (PbAc) treatment, the cell viability significantly decreased in a dose-dependent manner, and the accumulation of cellular ROS was observed. 8-OHdG levels, a marker of oxidative DNA damage, were significantly increased by both acute and chronic Pb exposure. Interestingly, the mRNA expression of the 8-oxoguanine DNA glycosylase 1 (hOGG1) significantly decreased after acute and chronic exposure. In conclusion, our study provides the first evidence to demonstrate that acute and chronic Pb exposure results in the altered expression of DNA glycosylases genes indicating the impairment of DNA repair pathways and contributing to DNA damage. These findings should be useful for the more comprehensive assessment of the toxic effects of Pb.
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铅诱导DNA糖基化酶表达减少和DNA氧化损伤
接触铅(Pb)仍然是一个重大的世界性问题。铅是一种剧毒的重金属,影响人体的几个器官系统。据报道,它对多种细胞具有潜在的遗传毒性。然而,铅致毒性的潜在机制仍不清楚。本研究旨在探讨铅致人肾近端小管上皮细胞的细胞毒性及其潜在的DNA损伤机制。即使在相对正常的剂量(10μg/dL)下,细胞中的8-OHdG/dG比值也会增加,这表明铅暴露导致DNA损伤。铅还导致氧化应激的产生,其特征是活性氧(ROS)指标的强度增加。活性氧过量产生应该是铅诱导DNA损伤的原因。因此,铅对ROS消除的影响可能是铅诱导人肾近端小管上皮细胞氧化应激的主要原因。经醋酸铅(PbAc)处理后,细胞活力呈剂量依赖性显著降低,细胞ROS积累明显。8-OHdG水平(DNA氧化损伤的标志)在急性和慢性铅暴露中均显著升高。有趣的是,8-氧鸟嘌呤DNA糖基酶1 (hOGG1)的mRNA表达在急性和慢性暴露后显著降低。总之,我们的研究提供了第一个证据,证明急性和慢性铅暴露会导致DNA糖基酶基因表达改变,这表明DNA修复途径受损,并导致DNA损伤。这些发现将有助于更全面地评价铅的毒性作用。
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来源期刊
Toxicology International
Toxicology International Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
0.60
自引率
0.00%
发文量
23
期刊介绍: Toxicology International is a peer-reviewed International Research Journal published bi-annually by the Society of Toxicology, India. The Journal is concerned with various disciplines of Toxicology including man, animals, plants and environment and publishes research, review and general articles besides opinions, comments, news-highlights and letters to editor.
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