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Transforming growth factor-beta 1 inhibits TCDD-induced cytochrome P450IA1 expression in human lung cancer A549 cells
1Medical Institute of Environmental Hygiene, Heinrich-Heine-University of Düsseldorf, Germany.
Abstract:
The effect of transforming growth factor-beta 1 (TGF-beta 1) on the expression of cytochrome P450IA1 (CYPIA1) was examined in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human lung cancer A549 cells. Using the reverse transcription-polymerase chain reaction (RT-PCR) it was demonstrated that TGF-beta 1 inhibits CYPIA1 expression in a dose dependent manner. Based on the inhibitory concentration 50 (IC50) of about 5 pM it is suggested that TGF-beta 1 has a physiological function in downregulation of this cytochrome. In the presence of cycloheximide, the effect of TGF-beta 1 on CYPIA1 mRNA disappeared. This finding indicates that protein synthesis may be required for the TGF-beta 1 mediated response of CYPIA1. The possible mechanisms by which TGF-beta 1 interacts with TCDD-responsive drug metabolizing enzymes are discussed.