An overview of rodent toxicities: Liver and kidney effects of fumonisins and Fusarium moniliforme

Fumonisins are produced by Fusarium moniliforme (= F. verticillioides) and other Fusarium that grow on corn worldwide. They cause fatal toxicoses of h orses and swine. Their effects in humans are unclear, but epidemiologic evi dence suggests that consumption of fumonisin-contaminated corn contributes to human esophageal cancer in southern Africa and China. Much has been lear ned from rodent studies about fumonisin B-1 (FB1), the most common homologu e. FB, is pearly absorbed and rapidly eliminated in feces. Minor amounts ar e retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause the same liver cancer promotion and subchronic (studies less than or equal to 90 days) liver and kidney effects as F. moniliforme. FB1 induces apoptos is of hepatocytes and of proximal tubule epithelial cells. More advanced le sions in both organs are characterized by simultaneous cell loss (apoptosis and necrosis) and proliferation (mitosis). Microscopic and other findings suggest that an imbalance between cell loss and replacement develops, a con dition favorable for carcinogenesis. On the molecular level, fumonisins inh ibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretica lly, sphingolipid-mediated regulatory processes that influence apoptosis an d mitosis. Liver sphingolipid effects and toxicity are correlated, and cera mide synthase inhibition occurs in liver and kidney at doses below their re spective no-observed-effect levels. FB1 does not cross the placenta and is not teratogenic in vivo in rats, mice, or rabbits, but is embryotoxic at hi gh, maternally toxic doses. These data have contributed to preliminary risk evaluation and to protocol development for carcinogenicity and chronic tox icity studies of FB1 in rats and mice.