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 e xpression of cytochrome P450IA1 (CYPIA1) was examined in 2,3,7,8-tetra chlorodibenzo-p-dioxin (TCDD)-treated human lung cancer A549 cells. Us ing the reverse transcription-polymerase chain reaction (RT-PCR) it wa s demonstrated that TGF-beta(1) inhibits CYPIA1 expression in a dose d ependent manner. Based on the inhibitory concentration 50 (IC50) of ab out 5 pM it is suggested that TGF-beta(1) has a physiological function in downregulation of this cytochrome. In the presence of cycloheximid e, the effect of TGF-beta(1) on CYPIA1 mRNA disappeared. This finding indicates that protein synthesis may be required for the TGF-beta(1) m ediated response of CYPIA1. The possible mechanisms by which TGF-beta( 1) interacts with TCDD-responsive drug metabolizing enzymes are discus sed.