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Title: FUMONISINS: CURRENT RESEARCH TRENDS IN DEVELOPMENTAL TOXICOLOGY

Author
item Voss, Kenneth
item GELINEAU-VAN WAES, JANEE - U.NEB.MED CEN., OMAHA, NE
item Riley, Ronald

Submitted to: Mycotoxin Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/5/2006
Publication Date: 7/1/2006
Citation: Voss, K.A., Gelineau-Van Waes, J., Riley, R.T. 2006. Fumonisins: current research trends in developmental toxicology. Mycotoxin Research 22(1):61-69.

Interpretive Summary: Fumonisin B1 (FB1) is a toxin made by Fusarium verticillioides, a mold that grows on corn. FB1 is found in corn-based foods worldwide. Some evidence suggests that eating food contaminated with FB1 or other fumonisins during early pregnancy increases the risk of neural tube defects (NTDs), serious birth defects that are often incompatible with life. The LM/Bc mouse strain is susceptible to NTDs caused by FB1 if the FB1 is given to the pregnant females by injection at a critical time during gestation. In contrast, FB1 does not cause NTDs in CD1 mice when it is given orally during pregnancy. To determine the suitability of the LM/Bc mouse model for studying the relationship between FB1 exposure and NTDs, it is important to find out if FB1 causes NTDs in one, but not the other type of mouse. Therefore, we fed diets containing FB1 to females of both strains. One of five litters from the LM/Bc group fed diets having 150 ppm FB1 was positive for NTD induction. NTDs were not found in the CD1 litters. In a second study, we gave FB1 to pregnant CD1 mice by injection at the critical time for NTD development. Forty percent of the litters from the females given 45 mg/kg body weight were NTD positive. In comparison, 100% of LM/Bc litters were affected at doses of 15 mg/kg body weight or greater. Therefore, we established that LM/Bc mice are not uniquely susceptible to induction of NTDs by FB1, however, they appear to be more sensitive than the CD1 strain. Studies to compare NTD induction in LM/Bc and CD1 mouse strains will be useful for determining the mechanism by which FB1 causes NTDs in mice and perhaps other species.

Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides that is found in corn and corn-based foods. Reproductive studies in CD1 mice, rats and rabbits initially found no evidence that fumonisins are teratogenic. However, more recent findings suggest that they might increase the risk of neural tube defects (NTDs) in populations consuming large amounts of fumonisin-contaminated corn. When > 15 mg/kg body weight fumonisin B1 (FB1) was given to pregnant LM/Bc mice by intraperitoneal (ip) injection, all litters were positive for NTDs. To determine if NTD induction is unique to the inbred LM/Bc mouse strain, NTD induction in LM/Bc and CD1 mice was compared: (a) in a study in which F. verticillioides culture material providing < 150 ppm FB1 was fed to female mice before and during gestation, and (b) in a study in which FB1 was given by ip injection to CD1 dams on gestation days 7 and 8, the critical time for NTD development. In the feeding study, one of five LM/Bc litters from dams fed the 150 ppm FB1 diet was positive for NTDs whereas no NTDs were found in the CD1 litters. In the ip injection study, 40% of the litters at the highest dose tested, 45 mg/kg body weight, were positive for NTDs and one of ten low-dose (15 mg/kg body weight) litters was also positive. Thus, FB1 induces NTDs in both LM/Bc and CD1 mice although the latter strain appears less sensitive. Comparative investigations using these strains will be useful for elucidating the mechanisms underlying fumonisin-induced NTDs in mice and determining the suitability of mouse models for studying the relationships between fumonisins and NTDs in humans.