Rat Liver DNA Synthesis during the “Catch-up” Growth of Nutritional Rehabilitation

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Abstract
When nutritionally rehabilitated, the malnourished suckling rat shows “catch-up” growth. This acceleration of growth rate was studied at the cellular level by measuring incorporation of tritiated thymidine into DNA and the activity of DNA polymerase. Changes in total liver DNA, protein, and protein/DNA ratio were also measured and related to changes in enzyme activity. After 11 days of postnatal malnutrition, total liver cell number (DNA content) was reduced to 55% of normal. Cell size (protein/DNA ratio) was unchanged. When these malnourished pups were refed, body and liver weight increased more rapidly than would be expected for their age, i.e. “catch-up” growth. After 10 days of refeeding, DNA content increased almost threefold without change in cell size. Thus refeeding induces hyperplastic liver growth. Tritiated thymidine incorporation into DNA was reduced to 24 to 53% of normal in the malnourished rats; within 2 days of refeeding incorporation had returned to normal and by 3 days was 38% above the normal levels. Thus the rate of cell division as measured by thymidine incorporation returned to normal by 2 days and was proceeding faster than normal by 3 days of refeeding. DNA polymerase activity “per cell” was 20 to 46% below normal between 11 and 14 days of age in the malnourished rats and increased to normal after only 12 hours of refeeding. Supranormal levels (180 to 190% of normal) were noted during days 1 to 3 of refeeding; by 4 days levels were returning to normal. The data show elevations in DNA polymerase activity from the reduced levels seen in malnutrition to normal or above normal values within the first 12 to 24 hours of refeeding, preceding, therefore, any measurable changes in radiothymidine uptake and DNA content.