A blood spot method for detecting fumonisin-induced changes in putative sphingolipid biomarkers in LM/Bc mice and humans

Ronald T. Riley, Jency L. Showker, Christine M. Lee, Cody E. Zipperer, Trevor R. Mitchell, Kenneth A. Voss, Nicholas C. Zitomer, Olga Torres, Jorge Matute, Simon G. Gregory, Allison E. Ashley-Koch, Joyce R. Maddox, Nicole Gardner, Janee B. Gelineau-Van Waes

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Abstract

Fumonisins (FB) are mycotoxins found in maize. They are hypothesised risk factors for neural tube defects (NTDs) in humans living where maize is a dietary staple. In LM/Bc mice, FB1-treatment of pregnant dams induces NTDs and results in increased levels of sphingoid base 1-phosphates in blood and tissues. The increased level of sphingoid base 1-phosphates in blood is a putative biomarker for FB1 inhibition of ceramide synthase in humans. Collection of blood spots on paper from finger sticks is a relatively non-invasive way to obtain blood for biomarker analysis. The objective of this study was to develop and validate in an animal model, and ultimately in humans, a method to estimate the volume of blood collected as blood spots on absorbent paper so as to allow quantification of the molar concentration of sphingoid base 1-phosphates in blood. To accomplish this objective, blood was collected from unexposed male LM/Bc and FB1-exposed pregnant LM/Bc mice and humans and applied to two types of absorbent paper. The sphingoid base 1-phosphates, absorbance at 270 nm (A270), and total protein content (Bradford) were determined in the acetonitrile:water 5% formic acid extracts from the dried blood spots. The results show that in both mouse and human the A270, total protein, and blood volume were closely correlated and the volume of blood spotted was accurately estimated using only the A270 of the extracts. In mouse blood spots, as in tissues and embryos, the FB1-induced changes in sphingolipids were correlated with urinary FB1. The half-life of FB1 in the urine was short (1.

Original languageEnglish (US)
Pages (from-to)934-949
Number of pages16
JournalFood Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment
Volume32
Issue number6
DOIs
StatePublished - Jun 3 2015

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All Science Journal Classification (ASJC) codes

  • Food Science
  • Chemistry(all)
  • Toxicology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Riley, R. T., Showker, J. L., Lee, C. M., Zipperer, C. E., Mitchell, T. R., Voss, K. A., Zitomer, N. C., Torres, O., Matute, J., Gregory, S. G., Ashley-Koch, A. E., Maddox, J. R., Gardner, N., & Gelineau-Van Waes, J. B. (2015). A blood spot method for detecting fumonisin-induced changes in putative sphingolipid biomarkers in LM/Bc mice and humans. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment, 32(6), 934-949. https://doi.org/10.1080/19440049.2015.1027746