|Gelineau-Van Waes, Janee -|
|Maddox, Joyce -|
|Gregory, Simon -|
|Ashley-Koch, Allison -|
|Torres, Olga -|
Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: January 1, 2012
Publication Date: March 11, 2012
Citation: Riley, R.T., Showker, A.J., Voss, K.A., Gelineau-van Waes, J., Maddox, J.R., Gregory, S.G., Ashley-Koch, A.E., Torres, O. 2012. Evidence for fumonisin inhibition of ceramide synthase in humans [abstract]. The Toxicologist (supplement to Toxicological Sciences). 126(1):237. Interpretive Summary: Abstract - no summary required.
Technical Abstract: Fumonisins are mycotoxins found in corn worldwide. Fumonisin B1 is the most common of the fumonisins. It is the cause of several farm animal diseases and is carcinogenic in rodents. Fumonisin B1 is poorly absorbed and is excreted primarily in feces and small amounts can be detected in urine. The mode of action is the inhibition of ceramide synthase a key enzyme in the biosynthesis of sphingolipids. Inhibition of ceramide synthase causes an accumulation of sphingoid bases and sphingoid base 1-phosphates in tissues and blood. In mice gavaged with fumonisin B1, sphinganine 1-phosphate (Sa1P) accumulates in red blood cells in a dose-dependent manner and there is an increase in the ratio of Sa1P/sphingosine 1-phosphate (So1P). The purpose of the present Institutional Review Board (IRB) approved study was to determine the relationship between fumonisin B1 in the urine and the Sa1P/So1P ratio in blood spots collected from women living in communities consuming large amounts of corn potentially contaminated with fumonisin B1. In the human study approximately 640 urine and blood spot samples were collected and analyzed from three locations in rural Guatemala (Chimaltenango, Escuintla, and Jutiapa) in March and June of 2011. Corn samples (n=57) from the same locations have been analyzed for fumonisins. The level of fumonisin in corn collected from local markets was significantly higher in Jutiapa compared to Chimaltenango or Escuintla. The urinary fumonisin B1 and the Sa1P/So1P ratio were also significantly higher in Jutiapa compared to Chimaltenango or Escuintla. The preliminary results show that fumonisin B1 in urine is significantly correlated with the increase in the Sa1P/So1P ratio in the blood spots. These results are consistent with the conclusion that fumonisin B1 disrupts sphingolipid metabolism in humans consuming large amounts of fumonisin B1 contaminated corn. Research supported by NIH grant # 1 RC4 HD067971-01.