Superinduction of cytochrome P1-450 gene transcription by inhibition of protein synthesis in wild type and variant mouse hepatoma cells.
Inhibition of protein synthesis superinduces transcription of the cytochrome P1-450 gene in Hepa 1c1c7 mouse hepatoma cells. The superinduced transcription rate is 10-15-fold higher than the maximal rate of transcription induced by the known inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone. Superinduction is maximal within 30-40 min and remains maximal for at least 90 min. Cytochrome P1-450 mRNA is the same length in TCDD-induced and superinduced cells. Superinduction does not occur in variant cells in which TCDD-receptor complexes bind weakly to nuclei and which do not transcribe the cytochrome P1-450 gene in response to TCDD. Inhibition of protein synthesis does not alter several properties of TCDD-receptor complexes. The results imply that a second control mechanism modulates the action of the TCDD-receptor complex in regulating cytochrome P1-450 gene transcription.
Israel
D I
DI
Estolano
M G
MG
Galeazzi
D R
DR
Whitlock
J P
JP
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D009693:Nucleic Acid Hybridization; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D014544:Uridine Triphosphate