Demonstration of in-situ apoptosis in mouse liver and kidney after short-term repeated exposure to fumonisin B1

Fumonisin B(1), a mycotoxin produced by Fusarium moniliforme, inhibits the activity of ceramide synthetase, the key enzyme in sphingolipid biosynthesis, leading to accumulation of sphinganine and sphingosine. Ceramide and other sphingolipid pathways have been implicated in signal-induced apoptosis in cells. Groups of male BALB/c mice received subcutaneous injections (0, 0.25, 0.75, 2.25 or 6.25 mg/kg) of fumonisin B(1) daily for 5 days and the liver and kidneys were sampled I day after the last injection. A decrease in kidney weight was observed after fumonisin treatment. A "blind" random evaluation of stained sections revealed dose-dependent fumonisin B(1)-associated hepatic and renal lesions in all groups. Terminal uridine triphosphate (UTP) nick-end labelling (TUNEL) in liver and kidney sections confirmed the presence of dose-related apoptotic cells at all treatment levels. Thus fumonisin B(1) produced apoptosis after a brief exposure to relatively low doses. The toxicity of fumonisin B(1) was greater than that previously found in studies on oral toxicity. (C) 1997 W.B. Saunders Company Limited.