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.


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 10mm.


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 maybe due to a reduction in the level of hydroxyl radicals.
Rao
M S
MS
Department of Pathology, Veterans Affairs Lakeside Medical Center, Chicago, Illinois, USA.
Subbarao
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage*; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003676:Deferoxamine / Q000008:administration & dosage*; D058607:Fibric Acids; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D002273:Carcinogens; D058607:Fibric Acids; D002995:Clofibric Acid; C019304:ciprofibrate; D003676:Deferoxamine