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Title: Evidence for inhibition of ceramide synthase by fumonisins in maize-based foods: studies in high- and low-exposure communities in Guatemala

item Riley, Ronald
item TORRES, OLGA - Molecular Diagnostic Laboratory
item MATUTE, JORGE - National Institute Of Public Health (INSP)
item GREGORY, SIMON - Duke University School Of Medicine
item ASHLEY-KOCH, ALLISON - Duke University School Of Medicine
item Showker, Adele
item Mitchell, Trevor
item MADDOX, JOYCE - Creighton University
item GELINEAU-VAN, JANEE - Creighton University
item Voss, Kenneth

Submitted to: International Symposium of Mycotoxicology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 9/27/2017
Publication Date: 11/30/2016
Citation: Riley, R.T., Torres, O., Matute, J., Gregory, S., Ashley-Koch, A., Showker, A.J., Mitchell, T.R., Maddox, J., Gelineau-Van, J., Voss, K.A. 2016. Evidence for inhibition of ceramide synthase by fumonisins in maize-based foods: studies in high- and low-exposure communities in Guatemala. International Symposium of Mycotoxicology Meeting. ISMYCO 2016, p 50.

Interpretive Summary:

Technical Abstract: Fumonisins (FB) are found predominantly in corn and corn-based foods. Fumonisin B1 (FB1) is the most common FB and causes species-specific diseases in animals including hepto- and nephrotoxicity in rodents and neural tube defects (NTDs; serious birth defects) in mice. The critical event in the mechanism of FB toxicity in animals is inhibition of ceramide synthase, which leads to disruption of sphingolipid metabolism and increased tissue concentrations of sphinganine, sphingosine and their sphinganine-1-phosphate (Sa1P) and sphingosine-1-phosphate (So1P) metabolites. The human health implications of FBs are not known although they are a suspected risk factor for cancer and NTDs in populations regularly consuming large amounts of foods containing FBs. To further study human FB exposure patterns, FB1 intakes in Guatemalan women (n=1240) from two low- and one high-FB exposure communities were compared using urinary FB1 (UFB1) as a putative biomarker of exposure. Sa1P, So1P, and the Sa1P/So1P ratio were also determined from whole blood samples collected from the women at the same time: samples were collected every three months from March 2011 to February 2012. LC-MS/MS analysis revealed that UFB1, Sa1P/ml blood, and blood Sa1P/So1P ratio were significantly higher in women living in the high-FB exposure community compared to those residing in the two low-FB exposure communities. These findings were corroborated in a second investigation (samples collected in February 2013) involving 300 women from a third low-FB exposure and two additional high-FB exposure communities. The correlations found between high FB1 intake and changes in blood Sa1P level and Sa1P/So1P ratio in these studies are consistent with those found in animals experimentally exposed to FBs, are evidence that FBs inhibit ceramide synthase in humans, and form a basis for further biomarker-based studies on FBs as potential risk factors for human disease.