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Rat Liver DNA Synthesis during the "Catch-up" Growth of Varied Nutritional Rehabilitation¹

Institute of Human Nutrition and Department of Pediatrics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032

When nutrionally rehabilitated, the malnourished suckling rat shows "catch-up" growth. This acceleration of growth rate was studied at the cellular level after varied nutritional rehabilitation by measuring the incorporation of tritiated thymidine into DNA and the activity of DNA polymerase. Changes in total liver DNA, protein and the protein/DNA ratio were also determined. Previously malnourished pups were "superfed" in litters of three and the outcome compared with previous data from pups "refed" in litters of 10 (1). Control animals were reared 10 pups per litter throughout. After 240 hours (10 days) of rehabilitation, both groups demonstrated purely hyperplastic growth. Liver DNA in "superfed" pups increased to 88% of control and to 80% of control in "refed" pups (P < 0.025). The increases in thymidine uptake and DNA content were preceded by elevations in DNA polymerase activity. Enzyme activity, employing denatured DNA as template/primer, was greater than control in both groups from 24 to 96 hours, but at 48, 72 and 96 hours "superfed" values were significantly higher (P < 0.02 or less) than "refed" values (percent of control: 262 versus 181, 255 versus 190 and 176 bersus 133, respectively). Thymidine uptake peaked significantly over control levels at 72 hours of rehabilitation in both groups, but by 120 hours the levels in "superfed" rats had returned to control values and those in "refed" rats had fallen to 30% below control (P < 0.025). After 240 hours of rehabilitation both radiothymidine uptake and DNA polymerase activity were significantly reduced in the two groups to at least 40% below control.

KEY WORDS: • DNA • DNA polymerase • thymidine uptake • malnutrition nutritional rehabilitation • "catch-up" growth • liver

¹ This research was supported in part by grants from the National Dairy Council and the National Institute of Child Health and Human Development (HD-07195).

² Dr. Jasper was a recipient of a fellowship from the Pan American Health Organization during the course of this work.

³ The present address of Dr. Jasper is: Hospital de Ninos, Division de Endocrinologia, Gallo 1330, Buenos Aires, Argentina.

⁴ Please address all reprint requests to Dr. Brasel at her present address: Jo Anne Brasel, M.D., General Clinical Research Center, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509.

Manuscript received 27 July 1979.