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Research Article Free access | 10.1172/JCI109410

Association of Poly(Adenosine Diphosphoribose) Synthesis with DNA Damage and Repair in Normal Human Lymphocytes

Nathan A. Berger, Georgina W. Sikorski, Shirley J. Petzold, and Kevin K. Kurohara

Division of Hematology-Oncology, Department of Medicine, Washington University School of Medicine at The Jewish Hospital of St. Louis, St. Louis, Missouri 63110

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Division of Hematology-Oncology, Department of Medicine, Washington University School of Medicine at The Jewish Hospital of St. Louis, St. Louis, Missouri 63110

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Division of Hematology-Oncology, Department of Medicine, Washington University School of Medicine at The Jewish Hospital of St. Louis, St. Louis, Missouri 63110

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Division of Hematology-Oncology, Department of Medicine, Washington University School of Medicine at The Jewish Hospital of St. Louis, St. Louis, Missouri 63110

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Published June 1, 1979 - More info

Published in Volume 63, Issue 6 on June 1, 1979
J Clin Invest. 1979;63(6):1164–1171. https://doi.org/10.1172/JCI109410.
© 1979 The American Society for Clinical Investigation
Published June 1, 1979 - Version history
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Abstract

A permeable cell technique was used to measure the alterations in synthesis of DNA and poly-(adenosine diphosphoribose) in normal human lymphocytes after treatment of the cells with different types of DNA-damaging agents. The lymphocytes showed an abrupt increase in the unscheduled synthesis of DNA and poly(adenosine diphosphoribose) in response to ultraviolet (UV) irradiation. The increases were apparent within 1 h and reached a maximum between 2 and 4 h after irradiation. The magnitude of the increases in DNA and poly(adenosine diphosphoribose) synthesis was dependent upon the UV dose. Alkaline CsCl gradient studies, with bromodeoxyuridine triphosphate density labeling of DNA, demonstrated that the unscheduled DNA synthesis, which occurred in response to UV irradiation, was actually a result of the repair mode of DNA synthesis. Similar increases in DNA synthesis, and poly(adenosine diphosphoribose) synthesis occurred when lymphocytes were treated with several other DNA-damaging agents, including bleomycin, N-methyl-N′-nitro-N-nitrosoguanidine or N-acetoxyacetyl aminofluorene. Treatment of lymphocytes with DNase, under conditions which allowed degradation of cellular DNA, also resulted in increased synthesis of poly(adenosine diphosphoribose). Cycloheximide did not inhibit the increase in synthesis of DNA or poly(adenosine diphosphoribose) that occurred in response to treatment with the DNA-damaging agents.

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