2. Academic Validation
  3. Effect of oxidative stress induced by 2,3,7,8- tetrachlorodibenzo-p-dioxin on DNA damage

Effect of oxidative stress induced by 2,3,7,8- tetrachlorodibenzo-p-dioxin on DNA damage

  • J Hazard Mater. 2024 Jul 5:472:134485. doi: 10.1016/j.jhazmat.2024.134485.
Chao Wang 1,  Xiaoxin Liu 2,  Junqiu Zhai 3,  Chunfei Zhong 1,  Haishen Zeng 2,  Longkuan Feng 2,  Yunyun Yang 4,  Xinyan Li 2,  Mei Ma 5,  Tiangang Luan 6,  Jiewei Deng 7
Affiliations

Affiliations

  • 1 Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China; Guangdong Provincial Key Laboratory of Water Quality Improvement and Ecological Restoration for Watersheds, School of Ecology, Environment and Resources, Guangdong University of Technology, Guangzhou 510006, China.
  • 2 Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China; School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
  • 3 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 4 Guangdong Provincial Key Laboratory of Chemical Measurement and Emergency Test Technology, Guangdong Provincial Engineering Research Center for Ambient Mass Spectrometry, Institute of Analysis, Guangdong Academy of Sciences (China National Analytical Center, Guangzhou), Guangzhou 510070, China.
  • 5 State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 6 Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China; School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Water Quality Improvement and Ecological Restoration for Watersheds, School of Ecology, Environment and Resources, Guangdong University of Technology, Guangzhou 510006, China; School of Environmental and Chemical Engineering, Wuyi University, Jiangmen 529020, China.
  • 7 Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China; School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. Electronic address: jwdeng@126.com.
PMID: 38701725 DOI: 10.1016/j.jhazmat.2024.134485
Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of Reactive Oxygen Species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O2.- and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O2.- and NO. In addition, transcriptome Sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast Cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.

Keywords

DNA damage; Oxidative stress; TCDD; Transcriptomic analysis.

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