INDUCTION OF APOPTOSIS BY FUMONISIN B-1 IN HT29 CELLS IS MEDIATED BY THE ACCUMULATION OF ENDOGENOUS FREE SPHINGOID BASES

Fumonisin B-1 (FB1) and aminopentol (AP(1)) (which is formed by hydrol ysis of FB1) are found in corn contaminated with some strains of Fusar ium moniliforme. Incubation of HT29 cells (a human colonic cell line) with FB1 or AP(1) caused a significant reduction in cell number; AP(1) was less potent, with 50 mu M AP(1) causing the same reduction (ca. 3 0% after 24 h) as 10 mu M FB1. The reduction in cell number reflected increases in DNA fragmentation and the percentage of apoptotic cells. Both FB1 and AP(1) caused the accumulation of sphinganine (25- and 35- fold by 10 mu M FB1 and 50 mu M AP(1), respectively); thus, concentrat ions of FB1 and AP(1) that caused comparable reductions in cell number were also similar with respect to elevation of sphinganine, a compoun d that is growth inhibitory and cytotoxic. Inhibition of the first ste p of sphingolipid biosynthesis with ISP-1 prevented the elevation in s phinganine, DNA fragmentation, and apoptosis induced by F-1. Therefore , these effects of FB1 on HT29 cells can be attributed to the accumula tion of sphinganine. Since consumption of food contaminated with Fusar ium moniliforme (Sheldon) exposes colonic cells to these mycotoxins, t he possibility that FB1 and AP(1) are toxic for intestinal cells in vi vo should be evaluated, especially in the light of the recent report ( Bhat et al., Clin. Toxicol. 35, 249, 1997) describing intestinal distu rbances in humans after consumption of moldy corn and sorghum containi ng fumonisins. (C) 1998 Academic Press.