Submitted to: Toxicological Sciences
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 2011
Publication Date: March 11, 2012
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J.B. 2012. Consumption of folate deficient diet did not increase neural tube defects in LM/Bc mice exposed to fumonisin B1. Toxicological Sciences. 126(1):238. Interpretive Summary: Abstract - no summary required.
Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides and F. proliferatum. It is found in corn and evidence suggests it is a possible risk factor for neural tube defects (NTD) in populations consuming large amounts of contaminated corn-based foods. The mechanism(s) underlying NTD induction by FB1 in the sensitive LM/Bc mouse is not well understood. However, partial reversal of NTD by co-exposure to folic acid and almost complete reversal by the complex sphingolipid GM1 suggests that disrupted folate utilization is involved. To further explore folate and NTD, female LM/Bc mice were fed a nutritionally sound control or a folate deficient diet starting 5 weeks before mating and continuing to embryonic day 16 (E16), when the litters were examined. Upon successful mating (E0), females were assigned to groups (3 groups/diet; n=9-13 dams/group) for treatment with 0 (vehicle), 2.5 or 10 mg/kg body weight FB1 (intraperitoneal injection) on E7 and E8. The folate deficient diet did not have any overt adverse effect on the dams. NTD were found in litters of control diet-fed dams treated with greater than or equal to 2.5 mg/kg FB1. The incidence of affected litters increased in a dose-dependent manner: 3 of 13 (23%) low dose and 10 of 11 (91%) high dose litters had greater than or equal to 1 NTD affected fetus. In contrast, NTD were found in the folate deficient diet groups only in 4 of 11 (36%) litters at 10 mg/kg FB1. In utero death rates including resorptions plus late fetal deaths were higher in the folate deficient diet groups than in their corresponding control diet groups, but increased embryolethality did not account for the differences in NTD incidence. The findings indicate that long-term consumption of folate deficient diet does not increase the likelihood of NTD following exposure of LM/Bc dams to FB1. Interactions between fumonisin exposure, folate-dependent processes, and NTD induction in the LM/Bc mouse model are complex and warrant further investigation.