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Effect of Protein Deprivation and of Starvation on DNA Synthesis in Resting and Regenerating Rat Liver¹

Istituto di Patologia Generale, Università di Bologna, 40126 Bologna, Italy

The effect of feeding a protein-free diet on DNA synthesis in vivo in normal and regenerating liver, and on the activity of two enzymes, DNA polymerase and thymidine kinase, which are supposed to be involved in this process was investigated. Regenerating liver from rats fed a protein-free diet for 7 days incorporated ²H-thymidine into DNA at about the same rate as controls, whereas in resting liver the DNA synthesis in vivo was markedly reduced by protein deprivation. In regenerating liver the supernatant DNA polymerase and the thymidine kinase activities increased in protein-depleted rats at about the same level as in controls. In resting liver, the protein-free diet led to a marked increase of thymidine kinase activity; the DNA polymerase activity was also increased when assayed with heat-denatured DNA as primer, but remained unchanged with native DNA. The effect on the DNA polymerase activity was not due to reduced food intake because the same results were obtained with pair-fed animals. The hepatic DNA synthesis in vivo was markedly reduced by 3 days of starvation; at this time, the supernatant DNA polymerase activity was not significantly modified, and became higher than controls only after 4 days of fasting.

KEY WORDS: • protein deprivation • starvation • DNA synthesis • DNA polymerase • thymidine kinase • liver

¹ Aided by a grant from the Consiglio Nazionale delle Richerche, Roma, Italy.

² On leave of absence from the Institute of Physiology, University of Modena, Italy.

Manuscript received 13 October 1971.