|Dombrink Kurtzman, Mary Ann|
|Merrill Jr, Alfred|
Submitted to: Journal of Toxicology and Applied Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: Fumonisins are mycotoxins produced by Fusarium moniliforme and commonly found in corn. Fumonisins interfere with the enzyme ceramide synthase, resulting in decreased synthesis of complex sphingolipids and accumulation of the lipid, sphinganine. In this study, a human colonic cell line was used to monitor the effect of fumonisin B1 (FB1) and hydrolyzed FB1 (hFB1) because consumption of food containing fumonisins would expose cells in the colon to these mycotoxins. Both compounds caused growth inhibition, but FB1 was approximately five-fold more potent than hFB1, in significantly reducing the number of cells and causing an increase in sphinganine. Further studies are needed to evaluate the possibility that FB1 and hFB1 are toxic for cells in the intestine.
Technical Abstract: Fumonisin B1 (FB1) and hFB1 (which is formed by hydrolysis of FB1) are found in corn contaminated with some strains of Fusarium moniliforme. Incubation of HT-29 cells (a human colonic cell line) with FB1 or hFB1 caused a significant reduction in cell number; hFB1 was less potent, with 50 uM hFB1 causing the same reduction (ca 30% after 24 h) as 10 uM FB1. The reduction in cell number reflected decreases in the % of cells in S phase, and increases in DNA fragmentation and the % apoptotic cells. Both FB1 and hFB1 caused the accumulation of sphinganine (25- and 35-fold by 10 uM FB1 and 50 uM hFB1, respectively); thus, concentrations of FB1 and hFB1 that caused comparable reductions in cell number were also similar with respect to elevation of sphinganine, a compound that is growth inhibitory and cytotoxic. Inhibition of the first step of sphingolipid biosynthesis with ISP-1 prevented the elevation in sphinganine, DNA fragmentation, and apoptosis induced by FB1, and restored the % of viable cells in S phase. Therefore, these effects of FB1 on HT-29 cells can be attributed to the accumulation of sphinganine. Since consumption of food contaminated with F. moniliforme (Sheldon) exposes colonic cells to these mycotoxins, the possibility that FB1 and hFB1 are toxic for intestinal cells in vivo should be evaluated.