Regulation of cytochrome P1-450 gene transcription by 2,3,7, 8-tetrachlorodibenzo-p-dioxin in wild type and variant mouse hepatoma cells.
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.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004147:Dioxins / Q000633:toxicity*; D014644:Genetic Variation; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012334:RNA, Neoplasm / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012334:RNA, Neoplasm; D003577:Cytochrome P-450 Enzyme System