Toxins produced by certain fungi commonly found in food crops and animal feed can cause animal cells to self-destruct through a mechanism known to cause disease in humans and livestock, according to a team of scientists at the University of California, Davis, and the University of Nebraska, Lincoln. These natural fungal toxins triggered the process of genetically controlled cell death known as "apoptosis" in animal cells during laboratory tests, report UC Davis plant pathologist David Gilchrist and colleagues. Their findings appear in the April 16 issue of the Proceedings of the National Academy of Sciences. In this unusual collaboration between experts in both plant and animal biotechnology, researchers examined the effects on animal cells of a new class of fungal toxins that occur in crop plants. Recently these toxins had been shown to cause disease in humans and livestock, and were known to be involved in plant disease. In this study, these toxins triggered the cellular suicide process of apoptosis in animal cells. "The initiation of apoptosis by these mycotoxins, which are widespread in food crops and animal feed, identifies a previously unrecognized mechanism underlying health risks for humans and livestock," said Gilchrist, associate director of the UC Davis Center for Engineering Plants for Resistance Against Pathogens. Gilchrist and colleagues were studying toxins produced by two fungi, Alternaria alternata and Fusarium moniliforme, that cause plant diseases in corn, tomatoes and other crops. The studies were done in hopes of better understanding how genes that are normally involved in plant development might affect the plant's susceptibility to disease. The toxins produced by Alternaria and by the quite different Fusarium mold are intriguingly similar in chemical structure. For several years these "fumonisin" toxins have been a concern for health and agricultural policy-makers because consumption of the toxins by animals has been shown to cause nervous system, kidney and liver damage; cell death and, in some cases, cancer in different animals consuming contaminated feed. Fumonisin-contaminated corn has been linked to esophageal cancer in humans and to a deadly brain disease in horses. Gilchrist and collaborating animal molecular biologists at the University of Nebraska, Lincoln, suspected that apoptosis -- a process of programmed cell death by which chemical signals trigger genes in the cell to begin destroying the cell -- might be the mechanism used by this group of toxins to disrupt normal cell function and cause disease in animals and plants. Since apoptosis had been well characterized in animal cells, but had not yet been shown to occur in plant cells, the researchers decided to test the effect of fumonisin and alternaria toxins when applied individually to animal cells. For this laboratory study they used samples of monkey kidney cells. Within a few hours after applying the toxins to the monkey cells, the researchers observed the abnormal DNA changes and cellular effects that are hallmarks of apoptosis. First, the DNA in the cell's nucleus broke up into specific, detectable fragments. Those fragments, along with other cellular components, were then organized into smaller units called apoptotic bodies before the cells disintegrated. In short, the cells self-destructed. Furthermore, the scientists also observed that the fumonisin toxin halted the cycle of cell division in the monkey kidney cells as those cells were dying. "It has been clear that fumonisin toxins pose a potentially serious health threat since corn and corn-based food products are a common staple in the diet of livestock animals and humans," said Gilchrist. "The results of this study indicate that apoptosis is one mechanism by which these chemicals can damage animal cells. But it is unclear at this time how chronic exposure to these toxins affects the health of animals and humans." The findings of this study are all the more compelling because fumonisin and alternaria toxins are related by chemical structure to sphinganine, a biochemically important compound found in both nervous system tissue and cell membranes. Sphinganine and related compounds also are potent signal molecules that can trigger expression of genes involved in apoptosis or programmed cell death. These results suggest that the toxic effects may be due to the structural similarity of the toxins to chemical cell regulators that normally exist in animals. (While this study was being conducted, the researchers also demonstrated that the alternaria toxins were triggering apoptosis in tomato plants during development of Alternaria stem canker disease. The results of that study, which for the first time identified apoptosis in plants, were published in the March 25 issue of the journal Plant Cell.) Collaborating with Gilchrist on this study were Hong Wang of Davis and Clinton Jones, Janice Ciacci-Zanella, Todd Holt and Martin B. Dickman of the University of Nebraska, Lincoln. Support for the study was provided by the National Science Foundation, which funds the UC Davis Center for Engineering Plants for Resistance Against Pathogens. The center focuses on the tomato as a research model to study fundamental mechanisms regulating disease in plants and to develop new technologies for engineering disease resistance in crop plants.