The effects of anti-oxidants were examined in Long-Evans Cinnamon (LEC) rats, which develop acute hepatic injury, and subsequent hepatic and renal tumors due to accumulation of excess Cu. The rats, at the age of 15 weeks, were supplied a diet containing either 1% of N-acetylcysteine (NAC), quercetin (QC), or phytic acid (PA), or basal diet alone. At weeks 2 and 6 posttreatment, animals were sacrificed for collection of blood and tissue samples. In the NAC-treated group, the development of hepatic and renal lesions was dramatically reduced. In addition, accumulation of Cu and Fe in the liver was suppressed. Acrolein-modified protein, a new marker for lipid peroxidation, was not detected in the liver or kidney of NAC treated rats, even though deposition was evident in control. Neither QC nor PA affected the development of spontaneous hepatic lesions. These results indicate that oxidative stress was reduced by NAC in the liver and kidney, and suggest that Cu and Fe may be involved in the generation of oxidative stress in the liver. In addition, it was suggested that the different effects of the anti-oxidants on lesion development in LEC rats might be related to different mechanisms of action with regard to oxidative stress.