ROLE OF OXIDATIVE STRESS IN THE MECHANISM OF DIELDRINS HEPATOTOXICITY

The production of reactive oxygen species (ROS) by toxic chemicals has been implicated in acute and chronic disease states, including cancer . This increase in cellular ROS call lead to a state of oxidative stre ss. Many compounds selectively induce hepatic tumors in mice but not r ats. The mechanism for the induction of hepatic cancer by these compou nds and the observed species selectivity of this effect are not known but may be related to the induction of oxidative stress. Dieldrin is o ne such compound and is used in the present study to characterize the relationship between oxidative stress and the observed selective hepat otoxicity of dieldrin in mice. It was found that dieldrin induced oxid ative stress in the mouse but not the rat, and the observed oxidative stress correlated with the induction of DNA S-phase synthesis. This ev idence suggests that the induction of oxidative stress may be a mechan ism by which dieldrin and other mouse specific compounds selectively i nduce their hepatic toxic effects in mice.