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EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON FETAL MOUSE URINARY TRACT EPITHELIUM IN VITRO
Citation:
Bryant, P. L., L. M. Reid, J E. Schmid, A R. Buckalew, AND B D. Abbott. EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON FETAL MOUSE URINARY TRACT EPITHELIUM IN VITRO. TOXICOLOGY. Elsevier Science BV, Amsterdam, Netherlands, 162(1):23-34, (2001).
Description:
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), produces hydronephrosis by altering the differentiation and proliferation of ureteric epithelial cells in the embryonic C57BL/6N mouse urinary tract. This study examines the effects of TCDD on late gestation fetal urinary tract cells using a in vitro model. Isolated ureteric cells from GD 18 fetal ureters were plated in medium supplemented with trace elements, a complex mixture of lipids, a defined mixture of purified hormones and growth factors. Both epithelial and mesenchymal cells remain viable under these conditions. The cultures were exposed to 0.1% dimethylsulfoxide (DMSO), 1 x 10-8, 1 x 10-9 or 1 x 10-10 M TCDD. Exposure to 1x10-8 M TCDD did not affect the cultures, while 1x10-8 M and 1x10-9 M TCDD supported epithelial, but not mesenchymal, cell survival and stimulated epithelial cell proliferation and differentiation. The TCDD-exposed cells expressed high levels of keratin and little or no vimentin, confirming that the cells which survive and differentiate are epithelial. However, after continuous exposure to EGF, the TCDD-induced stimulation of ureteric epithelial growth could not be detected. In conclusion, this study demonstrates thet late gestation ureteric cells respond to TCDD in vitro with stimulation of epithelial cell growth and differentiation, and that excess EGF mimics these responses.