Superinduction of cytochrome P1-450 gene transcription by inhibition of protein synthesis in wild type and variant mouse hepatoma cells

Abstract

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.