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Title: Evidence for ceramide synthase inhibition in humans exposed to fumonisins in maize-based foods and living in low or high exposure communities in Guatemala

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

Submitted to: Annual Meeting of the UNJR Panel on Toxic Microorganisms
Publication Type: Abstract Only
Publication Acceptance Date: 12/22/2015
Publication Date: 1/24/2016
Citation: Riley, R.T., Torres, O., Mutate, J., Grergory, S., Ashley-Koch, A., Showker, A.J., Mitchell, T.R., Maddox, J., Gelineau-Van Waes, J., Voss, K.A. 2016. Evidence for ceramide synthase inhibition in humans exposed to fumonisins in maize-based foods and living in low or high exposure communities in Guatemala. UJNR Toxic Microorganisms Panel Meeting. January 24-29,2016. Tokyo/Nagasaki, Japan.

Interpretive Summary:

Technical Abstract: Fumonisins (FB) are mycotoxins commonly found in corn and in foods made from corn. Fumonisin B1 (FB1), the most common FB, causes diseases in farm animals and causes liver and kidney toxicity and cancer in rodents. The key event in its mechanism of toxicity in animals is inhibition of the enzyme ceramide synthase. This inhibition in turn leads to disruptions of ceramide biosynthesis and sphingolipid metabolism. The latter includes increased tissue concentrations of sphinganine, sphingosine and their sphinganine-1-phosphate (Sa1P) and sphingosine-1-phosphate (So1P) metabolites. The human health effects of FB are uncertain. Exposure is however a suspected risk factor for cancer and neural tube defects (a type of serious birth defect) in populations that consume large amounts of corn-based foods containing FB as a dietary staple. To further evaluate FB exposure patterns in humans, studies were done to compare FB1 intake in Guatemalan women using urinary FB1 (UFB1) as a putative biomarker of exposure. In addition, Sa1P, So1P, and the Sa1P/So1P ratio were determined from whole blood spots that were collected on absorbent paper at the same time that the urine samples were obtained. Samples were collected every three months during March 2011 to February 2012 from a total of 1240 women residing in two low and one high FB intake communities. LC-MS/MS analysis showed that UFB1 as well as Sa1P/So1P ratio, and Sa1P/ml were significantly higher in the high intake community compared to the two low intake communities. The results were confirmed in a follow-up study in February 2013 that involved 300 women from another low exposure community and two additional high exposure communities. Taken together, the correlations between high FB1 intake and changes in blood Sa1P and Sa1P/So1P are evidence that FB inhibit ceramide synthase in humans and form the basis for biomarker-based epidemiological investigations on the role of FB as potential risk factors for human disease.