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Title: Evidence for Fumonisin inhibition of ceramide synthase in humans: validation in follow-up studies in Guatemala

Author
item Riley, Ronald
item Showker, Adele
item Voss, Kenneth
item GELINEAU-VAN WAES, JANEE - Creighton University
item MADDOX, JOYCE - Creighton University
item ASHLEY-KOCH, ALLISON - Duke University
item GREGORY, SIMON - Duke University
item MATUATE, JORGE - National Institute Of Public Health (INSP)
item TORRES, OLGA - National Institute Of Public Health (INSP)

Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: 1/17/2014
Publication Date: 3/23/2014
Citation: Riley, R.T., Showker, A.J., Voss, K.A., Gelineau-Van Waes, J., Maddox, J.R., Ashley-Koch, A.E., Gregory, S.G., Matuate, J., Torres, O. 2014. Evidence for Fumonisin inhibition of ceramide synthase in humans: validation in follow-up studies in Guatemala. Toxicologist. 138(1):86.

Interpretive Summary:

Technical Abstract: Fumonisins (FB) are mycotoxins found in corn. FB1 is the most common FB. It is the cause of farm animal diseases and is carcinogenic in rodents. The mode of action is the inhibition of ceramide synthase (CerS). Inhibition of CerS in mice causes a dose-dependent accumulation of sphinganine 1-phosphate (Sa1P) in blood and an increase in the ratio of Sa1P/sphingosine 1-phosphate (So1P). The purpose of this IRB approved study was to validate recent findings in Guatemala showing a significant direct correlation between urinary FB1 and the Sa1P/So1P ratio in blood spots collected from 1240 women in 2011 and 2012 from three separate departments, Chimaltenango (low FB intake), Escuintla (low FB intake) and Jutiapa (high FB intake). Based on a survey of FB in corn conducted in May to October 2012, three different departments were selected for the validation study: Sacatepéquez, Chiquimula and Santa Rosa. The average total FB in the corn from the three departments, respectively, was 1.0 mg/kg (n=48), 4.6 mg/kg (n=33), and 3.8 mg/kg (n=42). Approximately 300 urine and blood spot samples were collected in March and April 2013 from the three departments. Corn samples (n=30) from the same locations and times were collected and analyzed for FB to confirm low and high contamination. The level of FB in corn collected from local markets was significantly higher in Chiquimula and Santa Rosa compared to Sacatepéquez. The urinary FB1, the Sa1P/So1P ratio, and Sa1P/mg protein in blood spots were also significantly higher in Chiquimula and Santa Rosa compared to Sacatepéquez. This study confirms the findings of the earlier study. The results are consistent with the hypothesis that FB1 disrupts sphingolipid metabolism in humans consuming large amounts of FB contaminated corn. Supported by NIH grant # 1 RC4 HD067971-01.