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 altering the differentiation and proliferation of ureteric epithelial cells in the fetal C57BL/6N mouse urinary tract. This study tests the hypothesis that the late fetal urinary tract epithelial cells respond to TCDD with increased proliferation and that the responses do not require contributions from other maternal or fetal tissues. This was achieved by exposing late gestation fetal urinary tract cells to TCDD in an in vitro model. Isolated ureteric cells from gestation day (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), 1x10(-8), 1x10(-9) or 1x10(-10) M TCDD. Exposure to 1x10(-10) M TCDD did not affect the cultures, while 1x10(-8) 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 epidermal growth factor (EGF), the TCDD-induced stimulation of ureteric epithelial growth could not be detected. In conclusion, this study demonstrates that late gestational ureteric cells respond to TCDD in vitro with the stimulation of epithelial cell growth and differentiation.
Bryant
P L
PL
Environmental Sciences and Engineering Department, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Reid
L M
LM
Schmid
J E
JE
Buckalew
A R
AR
Abbott
B D
BD
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000378:metabolism / Q000633:toxicity*; D014551:Urinary Tract / Q000187:drug effects* / Q000196:embryology* / Q000473:pathology
D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D004815:Epidermal Growth Factor; D001973:Bromodeoxyuridine