Differential effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on nuclear RNA polymerase activity in the rat liver and thymus.
AN increase in RNA polymerase B activity in hepatic cell nuclei was observed after a single intravenous injection 1 microgram/rat of TCDD. The enzyme activity was about above the control value at 1 hr after injection and then declined rapidly. A secondary increase was evident at 24 hr. Prior to the secondary increase in RNA polymerase B activity, there was an increase in RNA polymerase A activity which was about 125% above the control value. The initial increase in RNA polymerase B activity was sensitive to both alpha-amanitin and actinomycin D injected min before TCDD administration. In the thymus, an increase in RNA polymerase B activity was observed 4 hr after injection (25% above control value) but thereafter it declined and at 24 hr it was about 30% below the control value. RNA polymerase A activity was inhibited as early as 1 hr after injection but had returned to the control value at 4 hr and then paralleled RNA polymerase B activity. Thus, TCDD stimulated RNA synthesis in the rat liver but the drug inhibited RNA synthesis in the rat thymus. Since these effects were detected as early as 1 hr after TCDD administration it is proposed that TCDD action requires transcriptional response and that this response may represent a primary site of TCDD action in the cell. The cellular entities or mechanisms which TCDD uses to alter transcription in the cell nucleus remain to be determined.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012321:DNA-Directed RNA Polymerases