The fumonisins are a series of mycotoxins produced by Fusarium moniliforme, a ubiquitous contaminant of stored corn (maize) worldwide. Consumption of food products contaminated with F. moniliforme has been correlated with increased risk of human esophageal cancer in epidemiological studies in southern Africa and China. The most abundant component, fumonisin B1 (FB1), was isolated from F. moniliforme culture extracts using a short- term tumor promoter bioassay to guide the fractionation. Purified FB1 has been confirmed to act as a tumor promoter in animal model systems; to cause hepatocellular carcinoma, cirrhosis and proximal tubule nephrosis in rats; and to mediate agriculturally significant diseases associated with consumption of F. moniliforme-contaminated feeds, including equine leukoencephalomalacia and porcine pulmonary edema. However, studies on the toxicokinetics of radiolabeled and unlabeled FB1 carried out by three research groups in five animal species all indicate that it is absorbed very poorly if at all when administered orally. There is no evidence for functionally significant metabolism of FB1 in vivo. These observations result in what might be called the 'fumonisin paradox' - how can the toxin cause agriculturally significant diseases and possibly human cancer if it is not effectively adsorbed after oral administration? There are several plausible explanations including (i) an unknown, readily bioavailable contaminating toxin is responsible; (ii) higher FB1 bioavailability at lower dose; (iii) greater conversion to active metabolites at lower dose; (iv) bioaccumulation and (v) effective uptake of FB1 derivatives that are readily converted back to FB1 or active metabolites in the body. The full extent of the threat to food safety posed by the fumonisins will not be known until the factors affecting oral bioavailability are understood.
Bibliographical noteFunding Information:
Research described in this review was supported in part by National Research Initiative Competitive Grants Program research grants 93-37201-9561 and 96-35201-3271 from the United States Department of Agriculture.
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.