Role of oxidative stress in the mechanism of dieldrin's 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 can lead to a state of oxidative stress. Many 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 but may be related to the induction of oxidative stress. Dieldrin is one such compound and is used in the present study to characterize the relationship between oxidative stress and the observed selective hepatotoxicity of dieldrin in mice. It was found that dieldrin induced oxidative stress in the mouse but not the rat, and the observed oxidative stress correlated with the induction of DNA S-phase synthesis. This evidence suggests that the induction of oxidative stress may be a mechanism by which dieldrin and other mouse specific compounds selectively induce their hepatic toxic effects in mice.
Bachowski
S
S
Armstrong Laboratory, Wright-Patterson AFB, OH 45433, USA.
Kolaja
K L
KL
Xu
Y
Y
Ketcham
C A
CA
Stevenson
D E
DE
Walborg
E F
EF
Klaunig
J E
JE
D000818:Animals; D000975:Antioxidants; D002273:Carcinogens / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D004026:Dieldrin / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D016877:Oxidants; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002273:Carcinogens; D009153:Mutagens; D016877:Oxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D004026:Dieldrin