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The first sphingosine-analog toxin was isolated in 1978 by Carter and Rinehart, who recognized both the analogy to sphingosine and its potential as a mechanism of action. However, interest in the field has expanded greatly since the recognition by Riley and associates that fumonisins, putative environmental tumor promoters that contaminate the food supply of hundreds of millions of people worldwide, are also sphingosine analogs. Sphingosine is a component of sphingolipids, some of which play structural roles (e.g., sphingomyelin), while others (sphingosine, ceramide and glycosphingolipids) appear to play important roles in cellular regulation. Sphingolipid analogs may act by altering normal sphingolipid metabolism, or by interacting as agonists or antagonists with sphingolipid-binding sites in regulatory processes. In the discussion that follows sphingosine analogs are classified as (i) simple sphingosine analogs isolated primarily from marine lower animals and characterized by either primary amines on linear chains or heterocyclic rings; (ii) myriocin-type analogs characterized by a 1-carboxylic acid moiety, which are antifungal agents produced by other fungi; (iii) fumonisins and AAL-toxins, a large but narrowly-defined structural class produced by phytopathogenic fungi; and (iv) vis-1-deoxysphingosines, which a tail-to-tail dimers obtained from marine lower animals. Ceramide analogs are classified as either simple ceramides or glycosphingolipids. These sphingosine and ceramide analogs exhibit a wide range of biological activities. [ABSTRACT FROM AUTHOR]

Aflatoxins present important food safely problems in both developed and developing countries. Contamination is monitored in developed countries using enzyme-linked immunusorbent assay(ELISA)- and high-performance liquid chromatography(HPLC)-based assays, both of which may be too expensive for routine use in many developing countries. There is a need for inexpensive alternative approaches to detect aflatoxins in lots of foods and feeds. Reviewed here are culture-based methods that determine if a sample is contaminated with aflatoxigenic fungi. These approaches include 1) blue fluorescence of aflatoxin B1, particularly when enhanced by includingβ-cyclodextrin in the culture medium, 2) yellow pigment production, and 3) color change on exposure to ammonium hydroxide vapor. The presence of aflatoxin B1 can be detected by its blue fluorescence, which is enhanced when the toxin complexes with the hydrophobic pocket ofβ-cyclodextrin. The yellow pigment and ammonium hydroxide vapor tests are based on the production of yellow anthraquinone biosynthetic intermediates in the aflatoxin pathway. These compounds act as pH indicator dyes, which are more visible when they have turned red at alkaline pH. Because these tests are based on two different mechanisms, it has been possible to combine them into a single test. In a study of 517 A. flavus isolates from the Mississippi Delta, the combined assay reduced false positives for aflatoxigenicity to 0%, and false negatives to 7%. The increased predictive power of the combined cultural assay may enable its use for inexpensively identifying potential aflatoxin contamination in feeds and foods. [ABSTRACT FROM AUTHOR]

Fumonisin B1 (FB1) is the most abundant of a series of sphingosine-analog mycotoxins produced by Fusarium verticillioides, the major fungal contaminant of stored corn (maize) world-wide. Fumonisins were originally isolated as environmental tumor promoters, and they remain a concern because they are frequent contaminants of corn-derived food products intended for direct human consumption. FB1 inhibits ceramide synthase, which may account for its acute toxic effects, but understanding of its tumor promotion mechanism has been limited by the general lack of understanding in the field. There is no evidence for functional metabolism of fumonisins in mammals, but abiogenic conversions during food processing are a concern because some known conversion products retain biological activity, including hydrolyzed FB1 (HFB1). HFB1, formed by alkaline removal of FB1 side chains, is a frequent contaminant of lime-treated corn products such as tortillas and tortilla chips. Humpf et al. (J. Biol. Chem., 273, 19060, 1998) observed that HFB1 not only inhibits ceramide synthase, but it is converted to a ceramide analog with about ten times the in vitro mammalian toxicity of intact FB1. In the present study we have confirmed this observation by preparing a series of ceramide analogs of HFB1 with varying fatty acid chain lengths and degree of unsaturation. Optimal in vitro mammalian toxicity was observed with fatty acid chain lengths of 10–14 carbons. However, ceramide analogs of HFB1 were not phytotoxic in vitro, and ceramide analogs of FB1 were not toxic in either mammalian or plant in vitro bioassays. [ABSTRACT FROM AUTHOR]

Fumonisins are a series of sphingosine-analog mycotoxins produced by Fusarium verticillioides, a ubiquitous contaminant of stored corn (maize) world-wide. Extensive alterations in the structures of fumonisins are possible without complete loss of in vitro toxicity. Numerous laboratories have reported that fumonisin B1 (FB1) levels in corn-derived foods are reduced during roasting and frying. We have conducted radiotracer studies to determine the fate of tritium-labeled FB1 added in laboratory models of corn flake manufacture (roasting), and tortilla chip manufacture (frying). These studies have confirmed that most, but not all, FB1 is converted to other substances during cooking. Under roasting conditions the major conversion pathway resulted in radiolabeled FB1 becoming covalently bound to proteins. Several lines of evidence supported a proposed role for FB1-anhydride, an intermediate formed by loss of water from a FB1 side chain, which enabled the toxin to bind covalently to proteins by reacting with amino groups. Under nixtamalization/frying conditions in preheated cooking oil, both FB1 and hydrolyzed FB1 were efficiently N-fatty acylated to the corresponding ceramide derivatives, presumably by fatty acid anhydrides or other degradation products formed from the fat by non-oxidative thermal degradation. The N-fatty acylated fumonisin derivatives were efficiently extracted from the chips into the hot oil. We will not understand the full threat to food safety posed by the fumonisins until we know what they are converted to during cooking, and what is the toxicity of those conversion products. [ABSTRACT FROM AUTHOR]

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 hasbeen 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 withconsumption 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. [ABSTRACT FROM AUTHOR]