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Rat Liver DNA Synthesis during the "Catch-up" Growth of Nutritional Rehabilitation^{1 ,2}

Division of Growth and Development, Institute of Human Nutrition, and Department of Pediatrics, Columbia University, College of Physicians and Surgeons, 511 West 166th Street, New York, New York 10032

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.

KEY WORDS: • postnatal malnutrition • DNA • protein • "catch-up" growth • DNA synthesis • radiothymidine uptake • DNA polymerase activity

¹ See NAPS document #02323 for 8 pages of supplementary material. Order from ASIS/NAPS, c/o Mierofiche Publications, 305 E. 46th St., New York, N. Y. 10017. Remit in advance for each NAPS accession number $1.50 for microfiche or $5.00 for photocopies. Make checks payable to Microfiche Publications. All foreign NAPS requests must include with prepayment a postage and handling fee of $2.00 per photocopy request or $0.50 per microfiche request.

² Supported in part by the National Institute of Child Health and Human Development, Grant #HD-07195 and the National Dairy Council.

³ Dr. Jasper was a recipient of a fellowship from the PAN AMERICAN HEALTH ORGANIZATION during the course of this work.

Manuscript received 20 July 1973.