TIME-RESPONSE AND DOSE-RESPONSE EFFECTS OF THE MYCOTOXIN, FUMONISIN-B-1 ON SPHINGOID BASE ELEVATIONS IN PRECISION-CUT RAT-LIVER AND KIDNEY SLICES

Fumonisins are mycotoxins produced on corn (Zea mays) by the common fu ngus Fusarium moniliforme. The fumonisins are potent inhibitors of sph ingolipid biosynthesis and cause dramatic elevations in the free sphin goid base, sphinganine, both in cells in culture and in urine, blood a nd tissues of animals dosed with the toxins. In this study the effects of fumonisin B-1 (FB1) on sphingoid bases in precision-cut rat liver and kidney slices were evaluated. In liver slices exposed for 20 hr to FB1, as little as 0.1 mu M caused a 40-fold elevation in free sphinga nine. Kidney slices were less responsive, and a 1 mu M dose of FB1 was required to cause a 10-fold increase in sphinganine. The amount of sp hinganine in liver slices exposed to FB1 increased in a time-dependent manner over a 72-hr period, but kidney slices exposed to the same dos es of FB1 showed a peak elevation of sphinganine after 24 hr, with a d ecline in the levels over the next 48 hr. Liver slices may more closel y approximate the in vivo response of animals to FB1 than do primary h epatocytes (in which sphinganine may be elevated >100-fold), because t he elevations in sphinganine were similar to those reported in livers of animals fed fumonisins. On the other hand, the response of kidney s lices to FB1 was substantially less than that reported in kidney tissu e of FB1-fed rats, suggesting that kidney may accumulate toxic levels of sphingoid bases that are released from other tissues into the blood . The use of tissue slices also appears to be a useful bioassay tool f or monitoring corn or other products for toxins, such as fumonisins, t hat elevate sphinganine levels. Crude extracts of corn screenings natu rally contaminated with fumonisins produced significantly elevated sph inganine levels in liver slices, even after 50-fold dilution of the ex tract. Copyright (C) 1996 Elsevier Science Ltd