Incidence of pancreatic and testicular tumors in rats treated with ciprofibrate, a peroxisome proliferator

It is hypothesized that hepatic tumors in rats induced by peroxisome proliferators is dependent on peroxisome proliferative effect of these compounds and the resulting oxidative stress. However, it is argued that since these compounds also induce tumors in pancreas and testes, the two organs in which there is no proliferation of peroxisomes, the carcinogenic effect is unlikely to be related to oxidative stress. To clarify this controversy we have systematically analyzed the incidence of pancreatic acinar cell foci and nodules, and testicular Leydig cell tumors in ciprofibrate treated and control rats. In animals treated with 0.025% ciprofibrate for 22 months the incidence of Leydig cell tumors and acinar cell lesions was 100% and 66%, respectively. In age-matched controls the incidence of testicular and pancreatic lesions was 93% and 66%, respectively. These findings clearly demonstrate that the Leydig cell tumors and pancreatic lesions develop spontaneously and are not induced by ciprofibrate.