Regulation of cytochrome P1-450 gene transcription by 2,3,7, 8-tetrachlorodibenzo-p-dioxin in wild type and variant mouse hepatoma cells.

Abstract

Using RNA synthesized in isolated nuclei, we have measured the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the rate of synthesis of cytochrome P1-450 mRNA in wild type mouse hepatoma (Hepa 1c1c7) cells and in variant (BPrc1) cells, which fail to accumulate the TCDD-receptor complex within the nucleus. In wild type cells, TCDD induces a 20-fold increase in the rate of synthesis of cytochrome P1-450 mRNA within 30 min. This effect persists for at least 18 h. In contrast, TCDD has no effect on cytochrome P1-450 mRNA synthesis in the variant cells. The results demonstrate that TCDD increases the rate of transcription of the cytochrome P1-450 gene and suggest that transcription requires nuclear localization of the TCDD-receptor complex.