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Title: THE USE OF GENETICALLY MODIFIED MICE FOR STUDYING THE IN VIVO MODE OF ACTION OF FUMONISINS: STUDIES ON TUMOR NECROSIS FACTOR ALPHA AND THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA.

Author
item Voss, Kenneth
item Riley, Ronald
item SHARMA, R - PHY/VET MED/UGA/ATHENS
item CORTON, J - TOXICOGENOM./CHAP.HILL/NC
item MILLER, J - CARLETON U./OTTAWA/CANADA
item Bacon, Charles

Submitted to: US-Japan Coop Pgm on Dev and Util of Natural Products Abstracts Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/15/2003
Publication Date: 1/30/2004
Citation: Voss, K.A., Riley, R.T., Sharma, R.P., Corton, J.C., Miller, J.D., Bacon, C.W. 2004. THE USE OF GENETICALLY MODIFIED MICE FOR STUDYING THE IN VIVO MODE OF ACTION OF FUMONISINS: STUDIES ON TUMOR NECROSIS FACTOR ALPHA AND THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA.. US-Japan Coop Pgm on Dev and Util of Natural Products Abstracts Proceedings. November 9 - 14, 2003. Tokyo, Japan.

Interpretive Summary: Abstract of presentation for UJNR - no summary required.

Technical Abstract: Fumonisins are mycotoxins that are found worldwide in corn and in corn-based foods. They are suspected human carcinogens and are the subject of ongoing risk assessments. Rodent feeding studies of fumonisin B1 (FB1) have been important for characterizing the toxicological effects of these mycotoxins for risk assessment. Important findings include: identifying the liver and kidney as target organs; characterizing FB1 induced lesions and the sequence of events during lesion development; proving that FB1 is hepato- and nephrocarcinogenic; and determining dose-response for these effects. Coordinated biochemical and toxicological investigations showed that FB1 inhibits the enzyme ceramide synthase and disrupts sphingolipid metabolism. Sphingolipids mediate cell growth and apoptosis and disrupted sphingolipid metabolism and apoptosis have been repeatedly correlated in vivo. Thus, ceramide synthase inhibition is a key step in the nongeno-toxic mode of action of fumonisins. Exposure assessments and understanding the fate of fumonisins during food production are also important for evaluating risk. The fate of FB1 during the production of masa and tortilla chips from corn was studied. Cooking and rinsing the corn in water, the first steps in masa production, led to significantly reduced fumonisin concentrations in the masa and tortilla chips. Baking and frying the masa to make the chips had little effect. Together, these toxicology and other data have contributed to risk assessments of fumonisins and the development of scientifically sound guidelines for their allowable concen-trations in corn used for food products.