FUMONISIN MYCOTOXINS

TOP FUMONISIN MYCOTOXINS Discovery of Fumonisins Human Exposure to Fumonisin How Fumonisins Kill Eat Your Bt Maize LITERATURE CITED

Fumonisins are mycotoxins produced by Fusarium molds, most notably Fusarium moniliforme (F. verticillioides) and Fusarium proliferatum. These mycotoxins occur as contaminants on agricultural products, particularly maize (Zea mays), in the field or during storage, worldwide. More than 10 types of fumonisins have been isolated and characterized. The most prevalent of these mycotoxins, which is also believed to be the most toxic, is fumonisin B-1 (FB-1). The facts that fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats (and probably humans), and disrupt sphingolipid metabolism, have resulted in much recent interest in these compounds (Marasas, 2001).

	Discovery of Fumonisins

TOP FUMONISIN MYCOTOXINS Discovery of Fumonisins Human Exposure to Fumonisin How Fumonisins Kill Eat Your Bt Maize LITERATURE CITED

Epidemiologists first raised the alarm that Fusarium-infested maize may be dangerous to the health of humans and livestock. A field outbreak of equine leukoencephalomalacia in South Africa in 1970 was associated with a high local incidence of F. moniliforme-infested maize. This fungus was also found to be prevalent on maize consumed by people in the Transkei region of South Africa, a high-incidence area for esophageal cancer. A strain of F. moniliforme isolated from moldy maize in Transkei was shown to cause leukoencephalomalacia in horses, as well as porcine pulmonary edema in pigs and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when FB-1, novel mycotoxin with cancer-promoting activity in rat liver, was isolated from culture material of F. moniliforme. Shortly thereafter, high levels of fumonisins in the 1989 U.S. maize crop resulted in large-scale field outbreaks of equine leukoencephalomalacia and porcine pulmonary edema in the United States. Subsequently, the fumonisins were found to occur naturally in maize and maize-based food products worldwide (Marasas, 2001).

	Human Exposure to Fumonisin

TOP FUMONISIN MYCOTOXINS Discovery of Fumonisins Human Exposure to Fumonisin How Fumonisins Kill Eat Your Bt Maize LITERATURE CITED

Humans are exposed to FB-1 primarily by the ingestion of contaminated maize (de Nijs et al., 1998). Although contaminated maize is the main culprit so far identified, there are increasing reports of its occurrence in other moldy crops as well (Logrieco et al., 1998; Martins et al., 2001). Most types of food processing do not affect the overall toxic effect, and fumonisin is detectable in food products ranging from corn flakes (De Girolamo et al., 2001) to beer (Hlywka and Bullerman, 1999). Although generally heat stable, fumonisin concentrations appear to decline as processing temperatures increase. However, the loss of fumonisins that does occur during very high-temperature processing is not necessarily a good thing: There is concern that fumonisin breakdown products may be more toxic than fumonisin itself (Bullerman et al., 2002).

Studies have shown that FB-1 intake is directly related to the quantity of maize consumed (de Nijs et al., 1998). Literature results concerning the occurrence of FB-1 in 349 samples of maize from 18 countries worldwide demonstrated the presence of this mycotoxin in 93% of the samples. The average contamination level was 1,359 ng of FB-1 per g of maize. Human intake of FB-1 was estimated based on the maize consumption of all people in the Netherlands in 1992. It was estimated that 1% are exposed to an intake of at least 10⁵ ng per person per day, and 49% to an intake of at least 10³ ng of FB-1 per person per day.

	How Fumonisins Kill

TOP FUMONISIN MYCOTOXINS Discovery of Fumonisins Human Exposure to Fumonisin How Fumonisins Kill Eat Your Bt Maize LITERATURE CITED

FB-1 structurally resembles sphingosine and is a specific inhibitor of ceramide synthetase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover (Riley et al., 2001). The most profound biochemical consequences of fumonisin are increased levels of free sphingoid bases and their 1-phosphates, and decreased ceramide biosynthesis. When free sphingoid bases accumulate, cells that are sensitive to sphingoid base-induced growth arrest will die and insensitive cells will survive. If the cells selected to die are normal phenotypes and the cells selected to survive are abnormal, then the risk of cancer increases.

Some studies have indicated that the effects of FB-1 may be gender specific. Howard et al. (2001) found that FB-1 induces renal tubule tumors in male rats (Rattus norvegicus) and hepatic tumors in female mice (Mus musculus). Bhandari et al. (2001) confirmed the high susceptibility of female mice to FB-1-induced hepatocarcinoma. The increased toxicity in females correlated with a greater increase of sphinganine and sphingosine levels in liver after FB-1 treatment compared to males.

Little is known about sphingolipids in plants, although available information suggests that these compounds (ceramide, sphingosine, and sphingosine-1-phosphate) may play important signaling roles in plants (see review by Ng and Hetherington, 2001). There are already suggestions that sphingolipid metabolites may be involved in such diverse processes as pathogenesis, the regulation of membrane stability, and the response of plants to drought (Ng and Hetherington, 2001). It is not too surprising, therefore, that FB-1 has been found to be highly toxic to plants (Abbas et al., 1992; Abbas et al., 1998; Moore et al., 1999).

	Eat Your Bt Maize

TOP FUMONISIN MYCOTOXINS Discovery of Fumonisins Human Exposure to Fumonisin How Fumonisins Kill Eat Your Bt Maize LITERATURE CITED

"Bt maize" refers to those maize cultivars that have been genetically engineered to express genes from the bacterium Bacillus thuringiensis that code for insecticidal proteins. Mechanical damage to maize kernels by feeding European corn borers (Ostrinia nubilalsi) often leads to Fusarium infection in the field. Bt maize hybrids have the potential to reduce fumonisin levels in field-harvested grain, by preventing the mechanical damage that results from the feeding of Bt-susceptible insects on ear tissues. Indeed, field experiments over the course of 3 years indicated that significantly less fumonisin occurred in Bt maize compared with nontransgenic hybrids (Munkvold et al., 1999). For example, in 1997, mean FB-1 concentrations in manually infested treatments were 11.8 µg g¹ for nontransgenic and 1.3 µg g¹ for transgenic hybrids. The higher fumonisin concentrations in nontransgenic hybrids were correlated with higher European corn borer populations during the early reproductive stages of the maize plants. These results indicate that under some conditions, genetic engineering of maize for insect resistance may enhance its safety for animal and human consumption. The general conclusions reached by Munkvold et al. (1999) have subsequently been confirmed by a number of independent researchers (Masoero et al., 1999; Dowd, 2000, 2001; Bakan et al., 2002): Genetically modified Bt maize is a healthier food alternative compared with traditional, nontransgenic, cultivars.