Chronic BDE-47 Exposure Induces DNA Damage in Hepatocytes: Involvement of Oxidative Stress and CYP1A1/2 Upregulation
TL;DR
BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.
Abstract
2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is a persistent food-chain pollutant targeting the liver, whose genotoxic potential remains poorly understood. Here we investigated BDE-47-triggered DNA damage using HepG2 cells and C3H/He mice. BDE-47 exposure markedly elevated DNA damage-related γ-H2AX foci in mouse liver. Cellular tests further validated BDE-47-induced DNA damage, manifested as elevated γ-H2AX foci, a higher comet tail DNA percentage, and a longer tail length. Mechanistically, BDE-47 activated the aryl hydrocarbon receptor (AHR) and raised hepatic reactive oxygen species (ROS) and malondialdehyde levels. In cellular assays, antioxidants alleviated DNA damage, whereas AHR inhibitors suppressed ROS overproduction. BDE-47 also upregulated hepatic CYP1A1/2, whose expression positively correlated with the severity of hepatic DNA injury in mice. In conclusion, BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.