DEMONSTRATION OF IN-SITU APOPTOSIS IN MOUSE-LIVER AND KIDNEY AFTER SHORT-TERM REPEATED EXPOSURE TO FUMONISIN B-1

Fumonisin B-1, a mycotoxin produced by Fusarium moniliforme, inhibits the activity of ceramide synthetase, the key enzyme in sphingolipid bi osynthesis, leading to accumulation of sphinganine and sphingosine. Ce ramide and other sphingolipid pathways have been implicated in signal- induced apoptosis in cells. Groups of male BALB/c mice received subcut aneous 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 t he last injection. A decrease in kidney weight was observed after fumo nisin treatment. A ''blind'' random evaluation of stained sections rev ealed dose-dependent fumonisin B-1-associated hepatic and renal lesion s in all groups. Terminal uridine triphosphate (UTP) nick-end labellin g (TUNEL) in liver and kidney sections confirmed the presence of dose- related apoptotic cells at all treatment levels. Thus fumonisin B-1 pr oduced apoptosis after a brief exposure to relatively low doses. The t oxicity of fumonisin B-1 was greater than that previously found in stu dies on oral toxicity. (C) 1997 W.B. Saunders Company Limited.