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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0022. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0022v1 100/3/845    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Buschfort-Papewalis, C. Articles by Thomale, J. Search for Related Content PubMed PubMed Citation Articles by Buschfort-Papewalis, C. Articles by Thomale, J. Related Collections Hematopoiesis and Stem Cells Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2002, Vol. 100, No. 3, pp. 845-853 HEMATOPOIESIS Down-regulation of DNA repair in human CD34+ progenitor cells corresponds to increased drug sensitivity and apoptotic response Claudia Buschfort-Papewalis, Thomas Moritz, Bernd Liedert, and Jürgen Thomale From the Institute of Cell Biology and Department of Internal Medicine, Center for Cancer Research and Cancer Treatment, University of Essen Medical School, Essen, Germany. Although DNA repair processes have been shown to considerably modulate the cytotoxic effects of alkylating agents, little information is available on the role of these mechanisms in chemotherapy-induced myelosuppression. Therefore, we have analyzed in detail the DNA repair capacity of primary human hematopoietic cells from cord blood (CB) or bone marrow (BM) by 2 functional assays, the immunocytologic assay (ICA) and single-cell gel electrophoresis (comet assay). Besides substantial interindividual differences, we consistently observed significantly lower repair capacity of CD34+ cells in comparison to CD34, CD19+, or CD33+ cells of the same donor. After exposure to the alkylating agent ethylnitrosourea (EtNU), the comet assay displayed on average twice as many DNA single-strand breaks (SSBs) in CD34+ cells and a tripled half-life of these lesions in comparison to corresponding CD34 cells. Similarly, reduced SSB repair activity in CD34+ cells was detected following melphalan or cisplatin application. When specific antibodies were used to monitor DNA reaction products of these drugs, adduct levels were significantly higher and lesions persisted longer in the CD34+ fraction. To assess the contribution of individual pathways to overall DNA repair, modulators blocking defined steps in repair processes were coapplied with alkylating drugs. Similar "modulation pattern" in corresponding CD34+ and CD34 cell fractions indicated a generalized reduction in DNA repair capacity of CD34+ cells, rather than deficiencies in a specific pathway. Because CD34+ cells also displayed higher frequencies of apoptosis in response to melphalan or cisplatin, these findings may help to explain the myelosuppression after exposure to alkylating agents. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Arab, M. Pedersen, J. Nair, M. Meerang, L. E. Knudsen, and H. Bartsch Typical signature of DNA damage in white blood cells: a pilot study on etheno adducts in Danish mother-newborn child pairs Carcinogenesis, February 1, 2009; 30(2): 282 - 285. 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