{"title":"Reduced DNA Glycosylases Expression and Oxidative DNA Damage Induced by Lead","authors":"Sirirak Hemmaphan, N. Bordeerat","doi":"10.18311/ti/2022/v29i3/29322","DOIUrl":null,"url":null,"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.","PeriodicalId":23205,"journal":{"name":"Toxicology International","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology International","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18311/ti/2022/v29i3/29322","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
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.
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.