RNA metabolism and poly(A) distribution in mouse liver following administration of dimethylnitrosamine |
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Authors: | M De Brabander F Aerts G Geuens R Van Ginckel R Van De Veire H Van Belle |
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Institution: | Janssen Pharmaceutica Research Laboratories, B-2340 Beerse Belgium |
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Abstract: | Dimethylnitrosamine (DMNA) strongly inhibited RNA synthesis in mouse liver under conditions when the nucleotide pattern, rate of nucleotide synthesis and phosphorylation ratio were unaffected. (An unidentified, probably non-nucleotide, component in the acid-soluble liver fraction was selectively reduced.) The inhibition of RNA synthesis was associated with a decrease in the RNA polymerase activity of isolated liver nuclei, well established already 45 min after DMNA administration. The reduced activity included both Mg2+- and Mn2+/(NH4)2SO4-stimulated polymerase functions. The inhibition in vivo involved the whole complement of RNA, including poly (A)-containing RNA and isolated poly(A) sequences. The transfer of labelled RNA from the nucleus to the cytoplasm was not impaired. There was no detachment of poly(A)-containing RNA from the microsomes, and the proportion of tightly membrane-bound microsomal RNA and poly(A) sequences was not reduced as determined by use of a flotation technique. No breakage or shortening of the poly(A) chains was indicated by sedimentation analysis. |
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Keywords: | GSH glutathione OMPI DL-2-oxo-3-(2-mercaptoethyl)-5-phenylimidazolidine |
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