l-owon. Vol 34. No. 5. pp. 527-534. 1996 Comneht c 1996 Elsev~er Science Ltd. All rights reserved Pergamon _ SOO41-0101(96)00007-4 Prmled ,n Great Br~tam 0041 0101~96$1500+000 DISRUPTION OF SPHINGOLIPID METABOLISM IN NON-HUMAN PRIMATES CONSUMING DIETS OF FUMONISIN-CONTAINING FUSARIUM MONILIFURME CULTURE MATERIAL G. S. SHEPHARD,’ L. VAN DER WESTHUIZEN,’ P. G. THIEL,’ W. C. A. GELDERBLOM,’ W. F. 0. MARASAS’ and D. J. VAN SCHALKWYK’ ‘Programme on Mycotoxins and Experimental Carcinogenesis. P.O. Box 19070, Tygerberg 7505. South Africa and ‘Business Informatics. Cape Technikon. P.O. Box 652, Cape Town 8000, South Africa (Recriwd 7 Notwthrr 1995; accepwd 3 Junuar~ 1996) G. S. Shephard. L. van der Westhuizen, P. G. Thiel, W. C. A. Gelderblom, W. F. 0. Marasas and D. J. van Schalkwyk. Disruption of sphingolipid metabolism in non-human primates consuming diets of fumonisin-containing Fusarium monifzforme culture material. Toxicon 34, 527-534, 1996.-The fumonisin mycotoxins are produced by Fusarium moniliforme Sheldon, a contaminant of corn worldwide. The two most abundant analogues (fumonisins B, and B?) are known to be potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) and hence to disrupt de nouo sphingolipid biosynthesis. The sphingoid bases,sphingosine and sphinganine (and hence their ratio), were measured at varying intervals over a period of 60 weeks in the serum of non-human primates (vervet monkeys; Cercopirlzecus aelhiops) which were consuming diets containing ‘low’ and ‘high’ amounts of F. monill~orme culture material, such that their total daily fumonisin intake was approximately 0.3 and 0.8 mg/kg body weight/day, respectively. Although no significant differences were found in the serumlevels of sphingosine compared to controls, serum sphinganine levels in the experimental groups (mean of 219 nM and 325 nM, respectively) were significantly (P = 0.02) elevated above the levels in controls (mean 46 nM). As a consequence,the ratio sphinganine:sphingosinewas significantly (P = 0.003) elevated from a mean of 0.43 in the control group to 1.72 and 2.57 in the experimental groups, respectively. Similar changes in sphingolipid profiles were also measuredin urine with an increase of the ratio from 0.87 in controls to 1.58 and 2.17 in the experimental groups, although the differences were not statistically significant. Hence, the disruption of sphingolipid biosynthesis in vervet monkeys by fumonisins in culture material added to their diet can effectively be monitored in the serum as an elevation of the sphinganine:sphingosine ratio. Copyright i, 1996 ElsevierScience Ltd. INTRODUCTION Ingestion of the fumonisin mycotoxins, produced in corn by Fusarium tnonil~forme Sheldon, has been shown to cause leukoencephalomalacia in horses (Kellerman et al., 527