Reduced DNA Glycosylases Expression and Oxidative DNA Damage Induced by Lead

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Authors

  • Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani − 12121 ,TH
  • Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani − 12121 ,TH

DOI:

https://doi.org/10.18311/ti/2022/v29i3/29322

Keywords:

DNA Damage, DNA Repair Genes, Human Renal Proximal Tubular Epithelial Cells, Lead, Reactive Oxygen Species (ROS) Production
Heavy metal toxicity

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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Published

2022-12-12

How to Cite

Hemmaphan, S., & Bordeerat, N. K. (2022). Reduced DNA Glycosylases Expression and Oxidative DNA Damage Induced by Lead. Toxicology International, 29(3), 321–328. https://doi.org/10.18311/ti/2022/v29i3/29322

Issue

Section

Research Articles
Received 2022-01-13
Accepted 2022-03-19
Published 2022-12-12

 

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