By J. Thomale, M. R. Müller, C. Buschfort, S. Seeber, M. F. Rajewsky (auth.), Prof. Dr. W. Hiddemann, Prof. Dr. T. Büchner, Prof. Doz. Dr. B. Wörmann, Prof. Dr. J. Ritter, Prof. Doz. Dr. U. Creutzig, M. Keating MD PhD, W. Plunkett MD PhD (eds.)
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Extra info for Acute Leukemias VII: Experimental Approaches and Novel Therapies
THOMALEl,M. MDLLER2,c. BUSCHFORT 1, S. SEEBER2,M. F. RAJEWSKy l Abstract. The sensitivity of human tumor cells to chemotherapeutic agents has recently been correlated to their ability to eliminate drug-induced DNA damage. However, the exact mechanisms by which specific DNA adducts cause cell death are still not fully understood nor are the relative efficacies of distinct pathways within the complex DNA repair network of mammalian cells. To elucidate the link between repair and drug resistance in primary cancer cells we have measured the functional DNA repair capacity of normal and leukemic human lymphocytes ex vivo.
As EtNU is a direct alkylating agent, the initial levels of DNA alkylation damage were homogeneous among all cells of a given sample and between individual cell specimens. , 06-etyhlguanine (06-EtGua [6,7]) and for secondary lesions (abasic sites and single strand breaks), induced by DNA repair processes, were considerably different for individual cell samples (Fig. 2). As measures for the cellular repair capacity we have calculated the required time periods after pulse exposure to EtNU to eliminate 50% of the DNA alkylation product (t50 ICA) or to 350 300 250 200 150 100 Fig.
Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA SERIU, T. Institute of Human Genetics, University of Heidelberg, 1m Neuenheimer Feld 328,69120 Heidelberg, Germany SIEBERT,R. Department of Human Genetics, Christian -Albrechts-University, Schwanenweg 24,24105 Kiel, Germany SKOTNICKI,A. Department of Hematology, Collegium Medicum, Jagiellonian University, ul. Kopernika 17, 31-50 1 Krakow, Poland SMIRNOVA, E. Department of Lymphosarcomas, Children's Onco-Hematological Center, F.