Structure-activity relationships of the corn fungal toxin fumonisin B₁: Implications for food safety

The cause of most human cancer is not known, but the preponderance of evidence implicates environmental agents. Almost all known environmental carcinogens have been shown to be mutagens, which suggests that they act as initiators of carcinoogenesis. In contrast, until the discovery of the fumonisins there were few, if any, viable candidates for environmental tumor promoters, agents which induce the subsequent step(s) of carcinogenesis. The fumonisins are a series of sphingosine-analog mycotoxins produced by the ubiquitous corn contaminant Fusarium moniliforme. The full extent of the threat to food safety posed by the fumonisins is not known, in part because much of the extractable, assayable fumonisin B₁ (FB₁) contaminating foods is converted to other unidentified forms during food processing. Structure-activity relationship studies on natural and synthetic fumonisins indicate that extensive alterations in structure are possible without loss of biological activity. This observation raised the concern that some of the FB₁ lost during food processing may actually have been converted to other biologically active forms. FB₁ is converted to other forms by several pathways under thermal food processing conditions. A major mechanism appears to be binding to protein, probably by conversion of a side chain to the anhydride followed by covalent coupling to protein by the mixed anhydride reaction.