http://www3.interscience.wiley.com/cgi-bin/abstract/98518446/ABSTRACT

Teratology
Volume 66, Issue 4 , Pages 169 - 176
Published Online: 25 Sep 2002

Copyright 2002 Wiley-Liss, Inc., A Wiley Company

Original Article

Prevention of fumonisin B1-induced neural tube defects by folic acid

T.W. Sadler 1 *, Alfred H. Merrill 2, Victoria L. Stevens 3, M. Cameron Sullards 2, Elaine Wang 2, Ping Wang 1
1Department of Cell and Developmental Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7090
2Department of Biochemistry, Emory University, School of Medicine, Atlanta, Georgia 30335-3050
3Department of Radiation Oncology, Emory University, School of Medicine, Atlanta, Georgia 30335-3801

email: T.W. Sadler (tsadler@med.unc.edu)

*Correspondence to T.W. Sadler, University of North Carolina, Department of Cell and Developmental Biology, 108 Taylor Hall, CB #7090, Chapel Hill, NC 27599-7090

Funded by:
NIH R01; Grant Number: HD29495, GM46368
March of Dimes; Grant Number: 1 FY00-802

Abstract

Background
The mycotoxin fumonisin B1 (FB1) inhibits sphingolipid synthesis, blocks folate transport, and has been associated with increased incidences of cancer and neural tube defects. Results from reproductive studies in animal models in vivo and in vitro have demonstrated toxicity in some cases, but no specific terata after fumonisin exposure. No information is available about folic acid's potential to protect against this toxicity.

Methods
Neurulating mouse embryos were exposed to fumonisin or folinic acid in whole embryo culture and assessed for effects on growth and development.

Results
Fumonisin exposure inhibited sphingolipid synthesis, reduced growth, and caused cranial neural tube defects in a dose dependent manner. Supplemental folinic acid ameliorated the effects on growth and development, but not inhibition of sphingolipid synthesis.

Conclusion
Fumonisin has the potential to inhibit embryonic sphingolipid synthesis and to produce embryotoxicity and neural tube defects. Folic acid can reverse some of these effects, supporting results showing that fumonisin disrupts folate receptor function. Teratology 66:169-176, 2002. 2002 Wiley-Liss, Inc.