Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on fetal mouse urinary tract epithelium in vitro

2,3.7,8-tetrachlorodibenzo-p-dioxin (TCDD), produces hydronephrosis by alte ring the differentiation and proliferation of ureteric epithelial cells in the fetal C57BL/6N mouse urinary tract. This study tests the hypothesis tha t the late fetal urinary tract epithelial cells respond to TCDD with increa sed proliferation and that the responses do not require contributions from other maternal or fetal tissues. This was achieved by exposing late gestati on fetal urinary tract cells to TCDD in an in vitro model. Isolated ureteri c cells from gestation day (GD) 18 fetal ureters were plated in medium supp lemented with trace elements, a complex mixture of lipids, a defined mixtur e of purified hormones acid 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 1 x 10(-10) M TCDD did not affect the cultures, while 1 x 10( -8) and 1 x 10(-9) M TCDD supported epithelial, but not mesenchymal, cell s urvival and stimulated epithelial cell proliferation and differentiation. T he TCDD-exposed cells expressed high levels of keratin and little or no vim entin, confirming that the cells, which survive and differentiate are epith elial. However, after continuous exposure to epidermal growth factor (EGF), the TCDD-induced stimulation of ureteric epithelial growth could not be de tected. In conclusion, this study demonstrates that late gestational ureter ic cells respond to TCDD in vitro with the stimulation of epithelial cell g rowth and differentiation. Published by Elsevier Science Ireland Ltd.