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Iron-dependent enhancement of polypeptide synthesis in hepatocellular carcinoma (HCC) cells in vivo and in vitro is a phenomenon that has been reported for the first time by our laboratory and elsewhere. As an example of enhanced translation, we studied inhibition of ornithine decarboxylase (ODC) activity and ODC translation in a rat hepatoma tumor model, Morris hepatoma 3924A. Hepatic ODC activity, translation, and protein synthesis were all enhanced by iron overload (due to an iron-rich diet). ODC activity was inhibited at a concentration of iron that enhances translation. Iron deprivation, by depletion with phenylhydrazine, did not restore ODC activity to that of the control, iron-deprived tumors. Hepatic protein synthesis was inhibited by iron deprivation to the same extent as was ODC activity, indicating that inhibition of ODC synthesis by iron deprivation occurs at the translation stage. Translation of polyribosomes isolated from iron-loaded hepatoma was two-fold above that of polyribosomes isolated from normal liver. Translation of liver polyribosomes from rats fed a «normal» diet (3.7-fold) or diet iron-deprived (3.8-fold) was not different from that of liver polyribosomes from rats fed an iron-rich diet (4.1-fold). Hepatic protein synthesis was enhanced by iron overload in animals fed an iron-rich diet. Hepatic protein synthesis was not elevated by iron deprivation of normal animals. Iron overload also enhanced translation of polyribosomes isolated from the liver. Experiments with cycloheximide demonstrated that iron deprivation increases protein synthesis, presumably by a stimulation of the elongation step. These experiments further demonstrate that a reductive change in iron level in vivo can cause a change in translation from
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