|Dresden-Osborne, Charissa - BIO SCI, CLEMSON U|
|Noblet, Gayle - BIO SCI, CLEMSON U|
Submitted to: Meeting, Center for Food Safety, University of Georgia
Publication Type: Abstract Only
Publication Acceptance Date: December 2, 2003
Publication Date: March 5, 2002
Citation: Voss, K.A., Riley, R.T., Dresden-Osborne, C., Noblet, G.P. 2002. FUMONISINS: UPDATE AND FUTURE RESEARCH NEEDS. Meeting, Center for Food Safety, University of Georgia. March 5 - 6, 2002. Atlanta, GA. Interpretive Summary: Abstract - presented to University of Georgia, Center for Food Safety, March 5-6, 2002, Atlanta, GA
Technical Abstract: Fumonisins are mycotoxins produced by Fusarium verticillioides (=F. moniliforme) and F. proliferatum. They are found worldwide in corn and corn-based feed and food products. Their impact on human health has not been established. However, correlations between F. verticillioides or fumonisins in homegrown corn and high rates of esophageal cancer in some populations in southern Africa and China, which depend on corn as a dietary staple, suggest that fumonisins may be a factor in human disease. Fumonisin B1 (FB1), the most commonly occurring fumonisin, was carcinogenic to rodents (studies conducted at the USFDA National Center for Toxicological Research, Jefferson, AR). Liver tumors were found in female B6C3F1 mice and kidney tumors were found in male Fischer 344 rats fed > 50 ppm FB1 for two years. The mechanism of action by which FB1 and other fumonisins exert their toxic and carcinogenic effects in animals has not been proven. Nonetheless, data obtained from a number of studies suggest that a) the mode of action is nongenotoxic; b) inhibition of the enzyme ceramide synthase is the key event in toxicogenesis; and c) a critical imbalance between cell death and replacement develops in affected tissues. These observations together with earlier findings concerning the toxicity of FB1 have provided dose-response, mechanistic and other critical data for evaluating the potential risk of fumonisin exposure. While the basic toxicology has been well characterized in rodents, a number of "future research needs" have been identified. These needs include studies to determine the effect of fumonisins on immune function. To this end, BALB/c mice were fed diets containing F. verticillioides culture material (CM) to provide 50 (LD group) or 150 (HD group) ppm fumonisins (FB1 + FB2) for 6 weeks. At these dose levels, the fumonisins inhibited tissue ceramide synthase activity, but caused only mild apoptosis in liver. A control group (ZD) was fed a diet lacking CM. After one week of CM (or control diet) exposure, the mice were challenged with the myotropic Brazil strain of Trypanosoma cruzi (103 parasites were given by ip injection), a parasite causing similar diseases in humans (Chagas' disease) and mice. Blood samples were periodically collected to evaluate parasitemia (0, 8, 14, 20, 26, 31 and 36 days after challenge). Five mice per group were killed on 0, 14, 26 and 36 days after challenge to determine heart and skeletal muscle parasite counts and to measure production of nitric oxide (NO) by peritoneal macrophages. Blood parasite counts of the groups were not different on days 0, 14, 20 and 36. However, the number of parasites found in the blood on days 26 and 31 was significantly reduced in the LD and HD groups and peak blood parasite counts in HD mice occurred earlier (day 20) than in the other groups (day 26). Parasite counts in cardiac muscle were decreased in LD and HD mice on days 14 and 26. While peak NO production by the HD and ZD groups was similar in magnitude, it occurred earlier in HD (day 14) than in ZD mice (day 26). Thus, host resistance to T. cruzi infection was enhanced in mice exposed to fumonisins and enhancement could be attributed, at least in part, to accelerated NO production by macrophages.