Abstract
AMONG the early toxic effects of various compounds on the liver cell which have been observed at the molecular level is disruption of the protein-synthesizing units or polysomes, resulting in decreased protein synthesis and a concomitant increase in the size of the single-ribosomal pool. Increased availability of the ribosomal surface of detached ribosomes for mRNA, detected indirectly by combining the artificial external coding agent poly U, has been reported to be the earliest metabolic effect on the liver cell of poisoning with carbon tetrachloride or dimethylnitrosamine1–3. The enhancement of poly U dependent protein synthesis was accompanied by decreased endogenous protein synthesis. On the other hand, chronic administration of various other compounds led to an increased rate of protein synthesis accompanying liver enlargement4. Hepatomegaly brought about in this way by the administration of food additives and other chemicals to rats may be toxic or hyperfunctional in origin5. Coumarin, a flavouring agent occurring in natural foods6,7, was found to be hepatotoxic8; chronic administration produced changes in the levels of several microsomal enzymes9 and, at millimolar concentration, decreased incorporation of ammo-acids by liver slices in vitro10. We reported earlier that coumarin administered in vivo stimulates the incorporation of labelled amino-acids in the liver11. We present here preliminary findings concerning the effects of coumarin treatment on the control of liver microsomal protein synthesis.
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NIEVEL, J., GOLBERG, L. Effect of Coumarin and other Compounds on Ribosomal Protein Synthesis in the Rat Liver. Nature 219, 858–860 (1968). https://doi.org/10.1038/219858a0
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DOI: https://doi.org/10.1038/219858a0
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