Transforming growth factor-beta 1 inhibits TCDD-induced cytochrome P450IA1 expression in human lung cancer A549 cells.
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.
Vogel
C
C
Medical Institute of Environmental Hygiene, Heinrich-Heine-University of Düsseldorf, Germany.
Döhr
O
O
Abel
J
J
D003513:Cycloheximide / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1