Toxicity and carcinogenicity of the Fusanum monilzforine metabolite, fumonisin B₁, in rats

Abstract

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.

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

“…FB 1 was isolated as the compound present in cultures of F. moniliforme MRC 826 that promoted the formation of preneoplastic altered enzyme foci in the livers of dimethylnitrosamine-initiated rats (22). In a subsequent study, including FB 1 at 50 mg/kg in the diet of BD IX rats led to development of liver tumors (23). Hepatic regenerative nodules, cholangiofibrosis, and cirrhosis developed in all 10 rats maintained on the FB 1 for 20-26 months, whereas only 7 of 10 rats developed hepatocellular carcinomas (23).…”

“…In a subsequent study, including FB 1 at 50 mg/kg in the diet of BD IX rats led to development of liver tumors (23). Hepatic regenerative nodules, cholangiofibrosis, and cirrhosis developed in all 10 rats maintained on the FB 1 for 20-26 months, whereas only 7 of 10 rats developed hepatocellular carcinomas (23). Although this study was limited to a single dose of FB 1 in the diet and included only a small number of rats, when combined with the tumor promotion studies (22) it strongly suggested that FB 1 was a rodent carcinogen.…”

Chronic Experimental Fumonisin Intoxication of Calves

“…Fumonisin (FB 1 ) is the most abundant of the fumonisins produced by F. moniliforme. The fumonisins cause encephalomalacia in horses 11 and pulmonary hypertension with pulmonary artery medial hypertrophy and right ventricular hypertrophy in swine, 4,21 are hepatotoxic in most animal species 3,[8][9][10]14,24 and carcinogenic in rats 6 and possibly people, 22 and are nephrotoxic in rats and rabbits. 8,24 Swine also exhibit altered myocardial function when exposed to fumonisins, and porcine cultured endothelium exhibits disruption of barrier function when FB 1 is present.…”

“…Equine piroplasmosis, dourine, and glanders are progressive, often fatal diseases of horses resulting from infections with Babesia equi or B. caballi, Trypanosoma equiperdum, and Burkholderia mallei, respectively. 1,[3][4][5][6]9 The Office of International Des Epizooties (OIE) classifies all 3 diseases as reportable List B conditions, and many OIE member nations maintain regulatory animal health controls to prevent the occurrence or spread of these diseases. 3 These controls often include a requirement that equids presented for importation be seronegative for each of the 4 infectious agents involved.…”

“…Many nations, including the United States, have maintained piroplasmosis-, dourine-, and glanders-free equine populations for many years. 1,3,6 Four separate complement fixation tests (CFT) are usually conducted for serodiagnostic purposes, 1 CFT for antibodies against each of the infectious agents. 2,3 The OIE also prescribes alternative test methods, and these must be used with sera that produce anticomplementary or otherwise spurious reactions in the CFT.…”