ToxSci Advance Access originally published online on November 4, 2003
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Toxicological Sciences 77, 165-171 (2004)
Copyright © 2004 by the Society of Toxicology
SYSTEMS TOXICOLOGY |
The Mycotoxin Fumonisin B1 Alters the Proliferation and the Barrier Function of Porcine Intestinal Epithelial Cells
* Laboratoire de Pharmacologie-Toxicologie, Institut National de Recherche Agronomique, 31931 Toulouse, France; and
Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, 00178 Roma, Italy
Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides (formerly F. moniliforme), a fungus that commonly contaminates maize. FB1 causes toxicological effects in laboratory and domestic animals including pigs. Because the gastrointestinal tract represents the first barrier met by exogenous food compounds, the purpose of this study was to investigate the effects of FB1 on IPEC-1, a porcine intestinal epithelial cell line. We first verified that low concentrations of FB1 did not exert any cytotoxic effect on IPEC-1. Indeed, significant LDH release was only observed for FB1 concentrations greater than 50 and 700 µM on proliferating and nonproliferating cells, respectively. We then demonstrated that FB1 inhibits proliferation of IPEC-1. Fluorescence-activated cell sorting (FACS) analysis of the cell cycle indicated that FB1 blocks the proliferation of intestinal cells in the G0/G1 phase. Similar results were obtained with LLC-PK1, a renal porcine epithelial cell line, which is considered to be a good model for studying FB1 in vitro effects. We have also assessed the effects of FB1 on the integrity of the barrier formed by the intestinal epithelium. We demonstrated that FB1 decreases the transepithelial electrical resistance (TEER) of IPEC-1 in a time- and dose-dependent manner. This effect was only noticed after a long exposure (8–12 days of treatment). FB1 induced the TEER decrease independently of the cell differentiation stage, and this effect was partially reversible. Taken together, our data indicate that FB1 alters the proliferation and the barrier function of intestinal cells. These results may have implications for humans and animals consuming FB1-contaminated food or feed.
Key Words: fumonisin B1; intestinal epithelial cells; IPEC-1; swine; barrier function; transepithelial electrical resistance.
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