Accession Number : ADA300102

Title :   Investigation into the Role of Oxidative Stress in the Mechanism of Dieldrin Hepatotoxicity in the B6C3F1 Mouse.

Descriptive Note : Doctoral thesis,

Corporate Author : AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH

Personal Author(s) : Bachowski, Stephen

PDF Url : ADA300102

Report Date : 25 OCT 1995

Pagination or Media Count : 273

Abstract : 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. 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 hepatocytes. In vivo experiments showed dieldrin to produce a dose- dependent and species-specific (mouse only) increase in hepatic malondialdehyde (MDA). Increases in urinary MDA and 8-hydroxy-2'- deoxyguanosine (oh8dG) were also observed in dieldrin treated mice. These increases coincided with the observed increase in DNA S-phase synthesis observed in mice. While dieldrin decreased hepatic Vit E in both mice and rats, no oxidative damage was observed in rats. Dieldrin induced oxidative stress in B6C3Fi mice was shown to be modulated by dietary Vit E.

Descriptors :   *STRESS(PHYSIOLOGY), *NEOPLASMS, *OXIDATION, *TOXIC AGENTS, *CANCER, STRESSES, PRODUCTION, DAMAGE, RATS, CHEMICALS, CELLS, TOXICITY, LIPIDS, REACTIVITIES, DEOXYRIBONUCLEIC ACIDS, OXYGEN, MICE, LIVER, CARCINOGENS, IN VIVO ANALYSIS, CELLS(BIOLOGY), INDUCTION SYSTEMS, MICROSOMES, DIELDRIN.

Subject Categories : Medicine and Medical Research
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE