Intravenous fumonisin B1 induces cell proliferation and apoptosis in the rat

Abstract

In the rat, the target organs of fumonisin B1, a mycotoxin produced by Fusarium moniliforme, are the kidney and liver. Fumonisin B1 is also hepatocarcinogenic in the rat and is associated epidemiologically with esophageal cancer in humans. We investigated the effect of a single intravenous dose of fumonisin B1 on cell proliferation, lesion development, and glutathione status in the major target organs of the rat. Male Sprague-Dawley rats were injected intravenously with fumonisin B1 at 0 or 1.25 mg/kg and were euthanized at 12 hr or, 1,2,3, or 5 days. An intraperitoneal injection of 5-bromo-2'-deoxyuridine at 100 mg/kg was given 90 min prior to euthanasia. In fumonisin B1 treated rats, serum cholesterol and serum urea nitrogen were elevated; however, the activity of hepatic enzymes was unaffected. Hepatic and renal glutathione concentrations were depressed at 12 and 24 hr, respectively, with subsequent recovery. Histologic changes were most prominent in the outer medulla of the kidney, with cell proliferation and apoptosis followed by nephrosis. Cell proliferation also occurred in the liver and esophagus, but in the absence of tissue injury. The labeling index peaked on day 1 for the liver and on day 3 for the esophagus. These results confirm that the primary target organ of fumonisin B1 in the rat is the kidney and support the concept that fumonisin B1-induced mitogenesis may be the mechanism of carcinogenesis.