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

A semi-purified corn-based diet containing 50 mg/kg of pure (not less than 90%) fumonisin B1 (FB1), isolated from culture material of Fusarium moniliforme strain MRC 826, was fed to a group of 25 rats over a period of 26 months. A control group of 25 rats received the same diet without FB1. Five rats from each group were killed at 6, 12, 20 and 26 months. The liver was the main target organ in the FB1-treated rats and the hepatic pathological changes were identical to those previously reported in rats fed culture material of F.moniliforme MRC 826. All FB1-treated rats that died or were killed from 18 months onwards suffered from a micro- and macronodular cirrhosis and had large expansile nodules of cholangiofibrosis at the hilus of the liver. Ten out of 15 FB1-treated rats (66%) that were killed and/or died between 18 and 26 months developed primary hepatocellular carcinoma. Metastases to the heart, lungs or kidneys were present in four of the rats with hepatocellular carcinoma. No neoplastic changes were observed in any of the control rats. Chronic interstitial nephritis was present in the kidneys of FB1-treated rats killed after 26 months. No lesions were observed in the esophagus, heart or forestomach of FB1-treated rats and this is contrary to previous findings when culture material of the fungus was fed to rats. It is concluded that FB1 is responsible for the hepatocarcinogenic and the hepatotoxic but not all the other toxic effects of culture material of F.moniliforme MRC 826 in rats.

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Fusarium moniliforme Sheldon is one of the most prevalent fungi associated with maize throughout the world. A correlation has been found between the incidence of F. moniliforme in home-grown maize and the human oesophageal cancer rate in Transkei, southern Africa. Culture material on maize of F. moniliforme strain MRC 826, isolated from maize in a high-risk area for oesophageal cancer in Transkei, was either freeze-dried or oven-dried and fed to groups of 20 inbred male BD IX rats on a life-long basis. At a dietary level of 8%, both types of culture material were hepatotoxic and caused 100% mortality. Hepatic lesions in rats that died were characterized by cirrhosis, nodular hyperplasia and bile-duct proliferation. At a dietary level of 4% for 286 days followed by 2% for the remainder of the experiment, both types of culture material were hepatocarcinogenic and caused hepatocellular carcinoma in 80% and ductular carcinoma of the liver in 63% of the rats surviving more than 450 days. Only one of 30 such rats did not have a primary hepatic carcinoma. No hepatocellular or ductular carcinomas occurred in the controls. Hepatocellular carcinomas in the experimental rats invariably developed in severely cirrhotic livers showing nodular hyperplasia. Adenofibrosis also developed concurrently with hepatocellular carcinoma. A higher incidence of basal cell hyperplasia occurred in the oesophageal epithelia of rats fed freeze-dried than in those fed oven-dried material. The chemical nature of the hepatotoxic and hepatocarcinogenic mycotoxin(s) produced by F. moniliforme is unknown.

Bovine tuberculosis (BTB) was first detected in Kruger National Park (KNP) in a single African buffalo (Syncerus caffer) in 1990. In 1991/1992, 2,071 African buffalo were examined for BTB as part of a culling program that removed animals from all known herds in KNP. The prevalence of BTB in 1991/1992 was estimated to be 0%, 4.4% (+/-0.6%), and 27.1% (+/-1.4%), in the north, central, and south zones of KNP, respectively. In 1998, a stratified, two-stage cluster sampling method was used to estimate that the prevalence of BTB was 1.5% (+/-2.5%), 16% (+/-5.3%), and 38.2% (+/-6.3%), in the north, central, and south zones, respectively. This represented a significant increase in prevalence (P < or = 0.05) in the south and central zones, but not in the north zone. Continued monitoring of BTB in KNP is important for understanding disease transmission risks, potential population effects, and the efficacy of disease management strategies. The methodology and sample sizes used in 1998 are appropriate for future BTB monitoring in KNP.