|Sharma, R - UGA/VET MED/PHYSIOL/PHARM|
|Merrill Jr, A - BIOCHEM/MED/EMORY U|
Submitted to: Symposium Proceedings
Publication Type: Proceedings
Publication Acceptance Date: December 20, 1999
Publication Date: March 1, 2000
Interpretive Summary: Fumonisins are poisons produced by molds that are commonly found on corn worldwide. They are produced primarily by a mold known as Fusarium moniliforme. Typically, the fumonisin B1 (FB1) level in processed corn products is very low. Nonetheless, levels of FB1 that can poison animals are sometimes found in corn-products and home-grown corn. High levels of fumonisins in feed are correlated with outbreaks of a brain disease in horses and a lung disease in pigs. The liver is a target in most animals and kidney is a target in some animals. FB1 does not appear to interact directly with the animals genes, however, it does cause cancer in rodents. When fumonisin kills cells, they die by a process that is sometimes called "cell suicide". This way of killing cells is unusual for a chemical that also causes cancer. It does not appear to be a poison that affects the reproductive process of animals unless the mother is poisoned. Fumonisin can also alter the way an animal responds to infectious agents such as viruses and bacterial toxins. One of the first things that fumonisin does to a cell is to change the way it makes a very unusual fat known as sphingolipids. All the toxic effects of the fumonisins seem to be very closely paralleled by changes in these unusual fats.
Technical Abstract: Fumonisins are fungal toxins commonly found on corn worldwide. They are produced by species of Fusarium, most notably Fusarium moniliforme. Typically, the fumonisin B1 (FB1) level in processed corn products averages < 1 ppm. Nonetheless, levels of FB1 > 5 ppm sometimes occur in corn-products and home-grown corn. High levels of fumonisins in feed are correlated with outbreaks of equine leucoencephalomalacia and porcine pulmonary oedema syndrome. The liver is a target in most species and kidney is a target in some species. FB1 is considered non- genotoxic but produced liver tumors in male BDIX rats and female B6C3F1 mice, and renal tumors in male F344N rats. Reproductive effects are secondary to maternal toxicity. FB1 induces apoptosis and alters cell growth, can modify immune response, inhibit the biosynthesis of receptors for pathogens and toxins, can sensitize macrophages to endotoxins, and alters cytokine expression in vivo. FB1 is an inhibitor of ceramide synthase, a key enzyme in sphingolipid biosynthesis. Inhibition results in an elevation in sphingoid bases and alters the amounts of the 1- phosphates and N-acetyl-derivatives of sphinganine. Disruption of sphingolipid metabolism is correlated with the animal toxicity and rodent carcinogenicity of FB1. FB1 also inhibits processes mediated by ceramide generated de novo. All of these changes must be considered when evaluating the effects of fumonisins.