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

• Published in: Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment Vol. 32; no. 6; pp. 934 - 949
• Main Authors: Riley, Ronald T., Showker, Jency L., Lee, Christine M., Zipperer, Cody E., Mitchell, Trevor R., Voss, Kenneth A., Zitomer, Nicholas C., Torres, Olga, Matute, Jorge, Gregory, Simon G., Ashley-Koch, Allison E., Maddox, Joyce R., Gardner, Nicole, Gelineau-Van Waes, Janee B.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.06.2015; Taylor & Francis Ltd
• Subjects: Animals; Biomarkers; blood spots; corn; Dried Blood Spot Testing; Estimating techniques; Female; fumonisin; Fumonisins - urine; Half-Life; Humans; LC-MS; Linear Models; Lysophospholipids - blood; maize; Male; Mice; Models, Animal; Phosphates; Pregnancy; Proteins; sphinganine 1-phosphate; sphingolipid; Sphingolipids - blood; Sphingosine - analogs & derivatives; Sphingosine - blood; Toxins; Zea mays; blood spots; LC-MS; fumonisin; sphingolipid; biomarkers; corn; sphinganine 1-phosphate; maize
• ISSN: 1944-0049; 1944-0057
• DOI: 10.1080/19440049.2015.1027746

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, FB 1 -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 FB 1 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 FB 1 -exposed pregnant LM/Bc mice and humans and applied to two types of absorbent paper. The sphingoid base 1-phosphates, absorbance at 270 nm (A 270 ), 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 A 270 , total protein, and blood volume were closely correlated and the volume of blood spotted was accurately estimated using only the A 270 of the extracts. In mouse blood spots, as in tissues and embryos, the FB 1 -induced changes in sphingolipids were correlated with urinary FB 1 . The half-life of FB 1 in the urine was short (<24 h) and the elevation in sphingoid base 1-phosphates in blood was also short, although more persistent than the urinary FB 1 .