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

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. TCDD is a highly toxic and carcinogenic pollutant known to cause genotoxic effects in organisms and cells. For the first time, fluorescence imaging and transcriptomic analysis were integrated to investigate the underlying mechanism of TCDD-induced genotoxicity. TCDD leads to the upregulation of genes associated with oxidative stress pathways, compromising the cellular antioxidant defense system, thereby increasing the production of O2.− and NO, and consequently inducing DNA AP site damage under oxidative stress conditions. This insight potentially contributes to elucidating the genotoxic mechanism of TCDD, which is crucial for evaluating its environmental hazards.