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Research Article Free access | 10.1172/JCI109094

Synthesis of DNA and Poly(Adenosine Diphosphate Ribose) in Normal and Chronic Lymphocytic Leukemia Lymphocytes

Nathan A. Berger, Jessie W. Adams, Georgina W. Sikorski, and Shirley J. Petzold

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

Washington University School of Medicine, St. Louis, Missouri 63110

Division of Allergy and Immunology, The Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri 63110

Washington University School of Medicine, St. Louis, Missouri 63110

Find articles by Berger, N. in: PubMed | Google Scholar

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

Washington University School of Medicine, St. Louis, Missouri 63110

Division of Allergy and Immunology, The Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri 63110

Washington University School of Medicine, St. Louis, Missouri 63110

Find articles by Adams, J. in: PubMed | Google Scholar

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

Washington University School of Medicine, St. Louis, Missouri 63110

Division of Allergy and Immunology, The Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri 63110

Washington University School of Medicine, St. Louis, Missouri 63110

Find articles by Sikorski, G. in: PubMed | Google Scholar

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

Washington University School of Medicine, St. Louis, Missouri 63110

Division of Allergy and Immunology, The Department of Pediatrics, St. Louis Children's Hospital, St. Louis, Missouri 63110

Washington University School of Medicine, St. Louis, Missouri 63110

Find articles by Petzold, S. in: PubMed | Google Scholar

Published July 1, 1978 - More info

Published in Volume 62, Issue 1 on July 1, 1978
J Clin Invest. 1978;62(1):111–118. https://doi.org/10.1172/JCI109094.
© 1978 The American Society for Clinical Investigation
Published July 1, 1978 - Version history
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Abstract

Peripheral blood lymphocytes were isolated from 9 patients with chronic lymphocytic leukemia (CLL) and 12 normal control donors. The cells were assayed for synthesis of DNA and poly-(adenosine diphosphate ribose) (poly[ADPR]) immediately after isolation and on successive days following their treatment with phytohemagglutinin (PHA). Two different techniques were used to measure DNA synthesis. In the standard technique, DNA synthesis was measured by incubating intact cells with [3H]deoxythymidine. In the new technique, the lymphocytes were first rendered permeable to nucleotides, then DNA synthesis was measured by incubating them with [3H]deoxythymidine triphosphate in the presence of deoxyATP, deoxyGTP, deoxyCTP, ATP, and Mg++. Both assays showed the anticipated rise in DNA synthesis after PHA stimulation of normal cells. PHA-stimulated lymphocytes from patients with CLL demonstrated low levels of DNA synthesis in both assay systems.

The initial levels of poly(ADPR) synthesis were greater in CLL lymphocytes than in normal cells. Studies with a T-cell-depleted population of normal cells showed the same activity for poly(ADPR) synthesis that was demonstrated by the original population of normal cells. PHA stimulation produced an increase in poly(ADPR) synthesis in both the normal and CLL cells. The increase in poly(ADPR) synthesis in normal cells was coincident with the increase in DNA synthesis. The increase in poly(ADPR) synthesis in the CLL cells was dissociated from the delayed and diminished increase in DNA synthesis. Thus, CLL cells have higher than normal initial levels of poly(ADPR) synthesis. Poly(ADPR) synthesis is dissociated from DNA synthesis in CLL cells whereas it varies directly with DNA synthesis in normal lymphocytes.

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