|Voss, Kenneth - Ken|
|Gelineau-van Waes, Janee|
Submitted to: Journal of the Japanese Association of Mycotoxicology
Publication Type: Proceedings
Publication Acceptance Date: 7/10/2005
Publication Date: 7/31/2005
Citation: Voss, K.A., Riley, R.T., Gelineau-van Waes, J. 2005. Trends in fumonisin research: recent studies on the developmental effects of fumonisins and fusarium verticillioides. Journal of the Japanese Association of Mycotoxicology/Mycotoxins. 55(2):91-100. Interpretive Summary: Fumonisins are toxins found in corn and corn-based foods. Fumonisin B1 (FB1) causes cancer in rodents and is a suspected human carcinogen. It has also been suggested that fumonisins are risk factors for birth defects known as neural tube defects (NTDs) in human populations heavily dependent on fumonisin-contaminated corn as a food source. Early experiments using the mouse strain CD1 gave no indication that fumonisins caused NTDs. Recently, however, an animal model for studying fumonisin's effect on fetal development has been developed using another strain, the inbred LM/Bc mouse. FB1 causes NTDs when given to pregnant LM/Bc mice. When folate (folate deficiency is a risk factor for NTDs) or GM1, a molecule associated with folate utilization in tissues, are given to the pregnant mice, the NTD rate in the fetuses is significantly reduced. We also compared the susceptibility of the LM/Bc and CD1 mouse strains to fumonisin-induced NTDs. Females were fed diets containing FB1 for 5 weeks, mated, and their litters examined. One of five LM/Bc litters was positive for NTDs while no NTDs were found in CD1 litters. Biochemical measurements provided evidence that FB1 crossed the placentas of the LM/Bc mice only, suggesting that exposure of LM/Bc fetuses to FB1 was greater than that of CD1 fetuses. Together, the findings suggest that physiological differences existing between these mouse strains influence their response to fumonisins. Comparative studies to characterize these differences will be useful for explaining how fumonisins cause NTDs in LM/Bc mice and to determine if fumonisins are a risk factor for NTDs in humans.
Technical Abstract: Fumonisins are mycotoxins found in corn and corn-based foods. Fumonisin B1 (FB1) causes cancer in rodents and is a suspected human carcinogen. FB1 inhibits ceramide synthase and increases sphingoid bases concentrations in tissues. It has recently been suggested that fumonisins are risk factors for neural tube defects (NTDs) in some human populations that are dependent on contaminated corn as a diet staple. However, NTDs were not found in in vivo developmental toxicity studies of fumonisins using rats, rabbits and CD1 mice. The LM/Bc mouse has recently been developed as a model for studying the developmental toxicity of fumonisins in vivo. Intraperitoneal injection of up to 5 to 20 mg/kg body weight FB1 to pregnant mice on gestation days 7.5 and 8.5 increased litter NTD incidence in a dose-dependent manner. Co-administration of folate or the complex sphingolipid GM1 with FB1 during gestation was protective, with GM1 being more effective. To compare susceptibility of the LM/Bc and CD1 mouse strains (used in earlier investigations)to fumonisin-induced NTDs, females were fed diets containing up to 150 ppm FB1 for 5 weeks, mated, and the litters examined after gestation day 15. One of five LM/Bc litters (dams fed 150 ppm FB1) was positive for NTDs whereas no NTDs were found in CD1 fetuses. Fetal liver sphingoid base concentrations were increased only in the LM/Bc strain. Fetal death occurred more often in the CD1 strain. These findings indicate that physiological differences between the two mouse strains influence their response to fumonisins. Comparative studies to elucidate these differences will be useful for elucidating fumonisin's mode of action in LM/Bc mice and further characterizing the potential risk of fumonisins for NTDs in humans.