The differential response of isolated intestinal crypt and tip cells to the inductive actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin

Abstract

The cell specific induction of uridine diphosphate(UDP)-glucuronyltransferase by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in intestinal epithelium was studied by administering [14C] TCDD (8 microgram/kg to adult female rats). Intact epithelial cells from the tip and crypt regions were isolated by differential vibration of rat duodenum. Cell separation was monitored by electron microscopy and marker enzymes. UDP-glucuronyltransferase and radioactivity were assayed in both cell types 0 h, 3 h, 10 h, 1 day, 3 days and 5 days after treatment. UDP-glucuronyltransferase activities were not significantly changed in either cell type isolated from TCDD-treated rats until 24 hr after treatment when a three-fold increase in crypt cell activity was evident. No significant changes in UDP-glucuronyltransferase activity were observed in the differentiated tip cells until 3 days after TCDD treatment. UDP-glucuronyltransferase was increased approximately two-fold in both cell types from 3 and 5 days following TCDD treatment. There was a negative correlation between the time-course of UDP-glucuronyltransferase induction and the [14C]TCDD concentrations measured in these cells. These studies suggest that the undifferentiated cells of the intestinal crypt region are more sensitive to TCDD inductive actions than are the absorptive tip cells.