FUMONISINS AS POTENTIAL CAUSES OF KIDNEY-DISEASE

The fumonisins are a series of sphingosine-analog mycotoxins produced by the ubiquitous corn (maize) contaminant Fusarium moniliforme. The m ajor component, fumonisin B-1 (FB1), has been shown to cause leukoence phalomalacia in horses, pulmonary edema in swine and hepatocellular ca rcinoma, cirrhosis and chronic interstitial nephritis in rats. Consump tion of corn-derived food products contaminated with F. moniliforme ha s been correlated with increased risk of human esophageal cancer in se veral epidemiological studies. High performance liquid chromatography (HPLC) assays using pm-column derivatization with fluorogenic reagents have been developed for FB1, and used to demonstrate that FB1 contami nates most corn and corn-derived processed food products intended for human consumption. Most types of food processing reduce FBI levels, bu t they do not completely eliminate it. A sensitive bioassay for mycoto xins, including FB1 and ochratoxins, has been developed using cytotoxi c effects on cultured mammalian cell lines of kidney origin. Cell line s which appear to have retained differentiated characteristics of tubu lar epithelial cells exhibit an unusual sensitivity to FB1 (about 10-f old increased sensitivity), which was not observed with other kidney-d erived cell lines, which appeared to be fibroblasts. Ochratoxins A and B exhibited similar cytotoxic effects with all kidney-derived cell li nes examined. Selective toxicity for tubular epithelial cells is consi stent with reported FB1 nephrotoxicity in rats. These observations rai se the concern that co-administration of fumonisins may alter the neph rotoxicity of ochratoxins and other nephrotoxic mycotoxins. This is of particular concern in Egypt, where FB1 contamination levels as high a s 3 mu g/g have been reported in corn, and daily consumption of >500 g of cereals is typical. Structure-activity relationship studies carrie d out on natural and synthetic fumonisins with this bioassay system in dicate that extensive alterations in structure ate possible without lo ss of biological activity. This observation raises the concern that FB I being eliminated during food processing may actually be getting conv erted to other biologically active forms. The full extent of the threa t to food safety posed by the fumonisins will not be known until it is determined what substances the toxin is converted to during food proc essing, and whether they retain biological activity. Similarly, it is doubtful if any rational approach to the removal of fumonisin contamin ation from foods can succeed without knowing which degradation process es lead to biologically active products.