2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN INCREASES MESSENGER-RNA LEVELS FOR INTERLEUKIN-1-BETA, UROKINASE PLASMINOGEN-ACTIVATOR, AND TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN UTERINE ENDOMETRIAL ADENOCARCINOMA RL95-2 CELLS

This study investigated the potential role of 2,3,7,8-tetrachlorodiben zo-p-dioxin (TCDD) in uterine growth utilizing a human endometrial ade nocarcinoma cell line (RL95-2), Western immunoblot analysis showed a m aximal induction of cytochrome P4501A1 (CYP1A1) at 1 nM TCDD, but no c hange in epidermal growth factor receptor (EGFR) protein level, Northe rn blot analysis showed that TCDD significantly increased the steady s tate mRNA level of CYP1A1 and CYP1B1 which was maximal at 1 nM. TCDD s ignificantly increased mRNA levels for interleukin-1 beta (IL-1 beta) by 6h, and for urokinase plasminogen activator (uPA) and tumor necrosi s factor-alpha (TNF-alpha) by 36h, Nuclear runoff analysis showed that transcription of CYP1A1 was significantly increased by TCDD with no e ffect on CYP1B1, uPA or IL-1 beta, These results indicate that TCDD ca n differentially alter the expression of growth factor and cytokine ge ne products in uterine cells which may contribute to the promotion of uterine disease. (C) 1997 Academic Press.