Investigation into the Role of Oxidative Stress in the Mechanism of DieldrinHepatotoxicity in the B6C3F1 Mouse

摘要

The production of reactive oxygen species (ROS) by toxic chemicals has beenimplicated in acute and chronic disease states, including cancer. This increase in cellular ROS can lead to a state of oxidative stress. Oxidative stress is a condition in which the pro-oxidant level within the cell exceeds the cell's capability to remove ROS or repair the damage they cause. Many organochlorinated compounds selectively induce hepatic tumors in mice but not rats. The mechanism for the induction of hepatic cancer by these compounds and the observed species selectivity of this effect are not known. It has been hypothesized that induction of oxidative stress may contribute to the observed hepatic toxicity and carcinogenicity of these compounds in mice. Dielcirin is one such compound and was used in this study to characterize the relationship between oxidative stress and the observed selective hepatotoxicity of dieldrin in mice. Mouse microsomes and hepatocytes showed an increase in the production ROS. This was not observed for the rat. Furthermore, dieldrin induced oxidative stress in mouse but not rat hepatocytes as evidenced by an increase in lipid peroxidation in mouse