The effect of deferoxamine on ciprofibrate-induced hepatocarcinogenesis in the rat

Background: Peroxisome proliferators (PP) are proven hepatocarcinogens in rats and mice. The carcinogenic effect of PP has been attributed to the oxidative stress that results from generation of high levels of hydrogen peroxide (H₂O₂). Since the hydroxyl radical is produced via metal mediated reaction from H₂O₂ and is DNA reactive, we have examined the effect of deferoxamine, the specific iron chelator, on ciprofibrate-induced hepatocarcinogenesis. Materials and Methods: Male F-344 rats were fed a diet containing ciprofibrate (0.025%) alone or ciprofibrate plus deferoxamine (0.3% or 0.6%) for 60 to 61 weeks, and the livers were analyzed for the incidence, number and size of the tumors. Results. One hundred percent of rats in all groups developed neoplastic nodules and hepatocellular carcinomas. However, in rats given a higher dose of deferoxamine there was a significant decrease in the number of tumors per liver and the number of tumors larger than 10 mm. Conclusions: Although deferoxamine did not prevent tumor development, at the higher dose level it caused a decrease in the number of tumors. These findings indicate that the decreased tumor numbers may be due to a reduction in the level of hydroxyl radicals.