In an extension of the experiment reported in the first paper of this series, the effects of dietary protein content on the glucose-6-phosphate dehydrogenase and pyrimidine reductase activities of rat liver and of Morris Hepatoma 5123 were studied in the same animals used for the other measurements.

All three of the enzymes studied were found to increase on high-protein diet and decrease on low-protein diet in normal rat liver, whereas the changes of these enzyme activities were suppressed remarkably in the liver of the tumor-bearing rats. In contrast, the pyrimidine reductases in Morris Hepatoma 5123 were absolutely insensitive to dietary protein change. Glucose-6-phosphate dehydrogenase in this tumor was influenced to some extent by increases in protein intake.

Additional experiments, with normal Holtzman male rats, confirmed the above results with control liver from Buffalo rats and suggested that, in the circumstances employed in these experiments, the enzymes studied, which were not related directly to protein metabolism, may have been limited by the supply of the protein building blocks to form them. In the light of these results and the concept of competition among metabolic changes, the relative insensitivity of the enzymes in Hepatoma 5123 and in host liver to dietary protein were discussed in relation to the derangement of protein metabolism in hepatoma-bearing animals.

Distinct sex differences opposite to those observed in control and host liver were demonstrated in the pyrimidine reductase and glucose-6-phosphate dehydrogenase in Morris Hepatoma 5123, and these sex differences were not reversed by the feminization of male host rats.

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This work was supported in part by a grant (No. C-646) from the National Cancer Institute, National Institutes of Health, U.S. Public Health Service.

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