Porphyria inducing drugs: comparative effects on nuclear ribonucleic acid polymerases in rat liver

H. L. Moses, T. C. Spelsberg, J. Korinek, F. Chytil

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4 Scopus citations

Abstract

Changes in δ aminolevulinic acid (ALA) synthetase activity, endogenous nuclear RNA polymerase activities (nucleolar and nucleoplasmic), and the availability of chromatin DNA to serve as template for RNA synthesis in rat liver in response to treatment with two porphyria compounds, allylisopropylacetamide (AIA) and 3,5 dicarbethoxy 1,4 dihydrocollidine (DDC), were determined. The alterations observed were compared with changes produced by two compounds that do not cause porphyria, phenobarbital (PB) and 3 methylcholanthrene (MC). Only AIA and DDC caused marked induction of ALA synthetase activity; PB caused a slight increase, and MC, no increase, in ALA synthetase. All four compounds caused some change in nuclear RNA synthesis in comparison with results in control animals given vehicle alone. AIA, DDC, and PB caused increased levels of RNA polymerase I (nucleolar) activity at time points later than 2 hr after injection, whereas MC resulted in a decreased level of RNA polymerase I activity at 8 and 12 hr. DDC, PB and MC also caused prominent modulations in RNA polymerase II (nucleoplasmic) activity, the values 8 hr after injection being considerably greater than in control livers. An elevation in endogenous polymerase II activity persisted at 12 hr only in the DDC and MC treated animals. These alterations in polymerase II activity for the most part can be explained by changes in chromatin template capacity. DNA dependent RNA synthesis using excess bacterial polymerase roughly paralleled the changes in polymerase II activity caused by DDC, PB and MC treatment. Conversely, AIA caused only minimal changes in either polymerase II or chromatin template capacity. These data and those from other laboratories suggest that AIA and DDC may have different primary sites of action in the induction of excessive quantities of ALA synthetase, the first and rate limiting enzyme in heme biosynthesis.

Original languageEnglish (US)
Pages (from-to)731-737
Number of pages7
JournalMolecular pharmacology
Volume12
Issue number5
StatePublished - Dec 1 1976

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Moses, H. L., Spelsberg, T. C., Korinek, J., & Chytil, F. (1976). Porphyria inducing drugs: comparative effects on nuclear ribonucleic acid polymerases in rat liver. Molecular pharmacology, 12(5), 731-737.