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.
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.
J Hazard Mater. 2024 Jul 5;472:134485. doi: 10.1016/j.jhazmat.2024.134485. Epub 2024 Apr 30.
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 O 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 O 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.
2,3,7,8-四氯二苯并对二恶英（TCDD）是一种具有高毒性的持久性有机污染物（POP），可在细胞内诱导 DNA 损伤。尽管氧化应激是导致 DNA 损伤的主要机制之一，但它在 TCDD 诱导的 DNA 损伤过程中的作用尚不清楚。在本研究中，同时监测了 TCDD 诱导的活性氧（ROS）的产生和 AP 位点的 DNA 损伤的发生。进一步的研究表明，TCDD 损害了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，破坏了细胞抗氧化防御系统。因此，这导致 O 和 NO 的产生增加，从而在氧化应激下诱导 AP 位点的 DNA 损伤。我们的发现通过上调碱基切除修复（BER）途径中的关键基因，并在抑制 O 和 NO 后不存在 DNA AP 位点损伤得到进一步证实。此外，转录组测序表明，TCDD 通过上调与 MAPK、环磷酸腺苷（cAMP）和乳腺癌途径中的氧化应激相关的基因来诱导 DNA 损伤。本研究为 TCDD 的毒性机制提供了重要的见解。
