Cultures on corn of Fusarium moniliforme MRC 826 are known to cause leukoencephalomalacia in horses and to be toxic and hepatocarcinogenic in rats. Culture material of this F. moniliforme isolate has also been shown to exhibit cancer-promoting activity in a short-term cancer initiation-promotion bioassay with diethylnitrosamine-initiated rats and the induction of gamma-glutamyl-transpeptidase-positive (GGT+) foci as an endpoint after 4 weeks of promotion. This bioassay was used as a monitoring system to isolate cancer-promoting compounds from cultures of F. moniliforme MRC 826. Culture material was successively extracted with ethyl acetate and CH30H-H20 (3:1). Most of the cancer-promoting activity was recovered in the CH30H-H20 extract and remained in the aqueous phase following partitioning of this extract between CH30H-H20 (1:3) and CHCl3. The CH30H-H20 fraction was chromatographed on an Amberlite XAD-2 column, and the active fraction was eluted with CH30H. This fraction was chromatographed on a silica gel column with CHCl3-CH30H-CH3COOH (6:3:1) as eluent and further purified on a C18 reverse-phase column. Two pure compounds were isolated, and these have been chemically characterized and given the trivial names fumonisin B1 and B2. At least 2 g of the major compound fumonisin B1 was purified from 1 kg of culture material. Fumonisin BI in the diet (0.1%) significantly (P < 0.001) induced the formation of GGT+ foci in the livers of initiated as well as noninitiated rats. The cancer-promoting effect of fumonisin B1 in rats was associated with a toxic effect, as evidenced by a significant (P < 0.0005) reduction in weight gain during the 4-week promoting treatment. The principal pathological change in rats treated with fumonisin B1 was an insidious and progressive toxic hepatitis similar to that induced by toxic culture material of F. moniliforme MRC 826. The toxicological effects of Fusarium moniliforme Sheldon in animals have been studied extensively (11). This fungus is known to cause leukoencephalomalacia (LEM) in horses (9) and to be highly toxic to a variety of experimental animals (5, 7, 8) and hepatocarcinogenic in rats (6, 10). Recently, corn samples naturally infected by F. moniliforme and implicated in field outbreaks of LEM in the United States have been reported to be hepatocarcinogenic in rats (14). These findings not only suggest that the LEM toxin and the hepatocarcinogen produced by F. moniliforme may be

The structures of the fumonisins, a family of structurally related mycotoxins isolated from cultures of Fusarium moniliforme, were elucidated by mass spectrometry and 1H and 13C n.m.r. spectroscopy as the diester of propane-lr2,3-tricarboxylic acid and either 2-acetylamino-or 2-amino-1 2,16-dimethyl-3,5,10,14,15-pentahydroxyicosane as well as in each case the C-10 deoxy analogue; in all cases both the C-14 and C-15 hydroxy groups are involved in ester formation with the terminal carboxy group of propane-I ,2,3-tricarboxylic acid.

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The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826. Fumonisin B1 (FB1), the major fumonisin produced in culture, has been shown to be responsible for the major toxicological effects of the fungus in rats, horses and pigs. Recent investigations on the purification of compounds with chromatographic characteristics similar to FB1 have led to the identification of two new fumonisins, FB3 and FB4. Fumonisins A1 and A2, the N-acetyl derivatives of FB1 and FB2 respectively, were also purified and shown to be secondary metabolites of the fungus. Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05-0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals. In contrast, no biological activity could be detected for FA1 under identical experimental conditions. These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens.