Protein Deficiency: Contrasting Effects on DNA and RNA Metabolism in Rat Liver

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Abstract
The early effects of protein-calorie malnutrition on synthesis of liver DNA and RNA were studied in the rat. Animals of the Sprague-Dawley strain were given protein-deficient (3.5% protein) and control (26% protein) diets between 28 and 42 days of age, the period from weaning to sexual maturation. Within 12 hours of initiation of the low protein diet, DNA synthesis, measured by incorporation of 3H-thymidine into DNA and activity of thymidine kinase, decreased to less than half of control values. The values remained in this range for the remaining 14 days. In contrast, incorporation of 14C-orotate into RNA increased to about double the control value, and uridine kinase activity became significantly increased by 2 days. Most of the DNA synthesis in the cell takes place in the nucleus, in preparation for cell division. A much smaller percentage is produced in mitochondria, where it is believed to control the relatively rapid proliferation of this self-replicating organelle, which is essential for production of cellular energy. Although incorporation of 3H-thymidine into nuclear DNA decreased to less than 50% of control values within 12 hours, incorporation into mitochondrial DNA remained stable for 2 days and then increased to more than double the control value at 14 days. There was a corresponding difference between nuclear DNA polymerase activity which remained almost unchanged, and mitochondrial DNA polymerase which increased in activity to more than three times the control value at 14 days. The results indicate a very prompt and sustained decrease in certain synthetic processes necessary for cell proliferation, whereas those related to energy production and protein synthesis either remained normal or were increased. These adaptations would favor the preservation of function in the liver cell at the expense of growth or increase in cell number.