|Gelineau-van waes, J|
|Voss, Kenneth - Ken|
Submitted to: International IUPAC Symposium on Mycotoxins and Phycotoxins
Publication Type: Abstract only
Publication Acceptance Date: 4/30/2004
Publication Date: 5/15/2004
Citation: Riley, R.T., Gelineau-Van Waes, J., Voss, K.A., Sharma, R.P., Haschek, W.M., Constable, P.D. 2004. Toxicology of the fumonisins and neural rube defects (NTD)[abstract]. International IUPAC Symposium on Mycotoxins and Phycotoxins. p. 91. Interpretive Summary: Abstract only - no interpretive summary required.
Technical Abstract: There is a great deal of information regarding fumonisin (FB) induction of equine leukoencephalomalacia, porcine pulmonary edema , nephrotoxicity and hepatotoxicity in many species, and nephrocarcinogenicity and hepatocarcinogenicity in rodents. In addition, it is well documented that FB disrupts lipid metabolism in all species. While the proximate cause and end results are well established, the intermediate events are not. For example, what is the basis for the species-specific effects in horses and pigs and the sex-, species- and strain-specific effects for carcinogenicity in rodents? While FB1 is a complete carcinogen, what is the cause of the DNA changes leading to transformed cells? The fact that toxicity is a prerequisite for carcinogenicity and antioxidants are protective suggests that oxidative damage could contribute to the carcinogenicity. Recent advances have been made in our understanding of the pathophysiological and biochemical events leading to ELEM and PPE, where disruption of cardiovascular function plays an important role. FB-induced disruption of sphingolipid metabolism has been reported in all species that have been studied. Recent work has focused on sphingoid base 1-phosphates, FB resistant ceramide synthase, and other enzymes in sphingolipid metabolic pathways. The relationship between toxicity, FB1-induced alterations in various signaling pathways, and cytokine expression are also being explored. While progress has been made in our understanding of FB induced animal diseases, FB involvement in human disease is poorly understood. Until recently, the proposal that FB1 could cause NTD was weak. However, there is now clear evidence that FB can induce NTD in LMBc mice. The fact that the NTD can be reduced with folate supplementation, and almost completely prevented with ganglioside GM1, provides support for the possible involvement of FB as a contributing factor to NTD in humans where FB contamination of maize and folate deficient diets are likely.