Title
Detection of single-strand breaks and base damage in DNA of blood cells from leukaemia patients receiving chemo- and radiotherapy
Author
van Loon, A.A.W.M.
Raadsheer, F.C.
Timmerman, A.J.
Haanen, C.
Wessels, J.
van der Schans, G.P.
Lohmans, P.H.M.
Baan, R.A.
Medisch Biologisch Laboratorium TNO
Publication year
1992
Abstract
Chemotherapy combined with total-body irradiation (TBI), a conditioning regimen for bone-marrow transplantation (BMT), causes lesions in the cellular DNA of the patients treated. To understand possible consequences of the DNA damage induced during such treatment, information is required about the nature of the damage, the level of induction and its persistence, and about the importance of the various lesions for cell-lethality and/or mutation induction. Recently, we developed a sensitive immunochemical method to quantify single-strand breaks (SSB) in the DNA of mammalian cells. In addition, a modification of the so-called alkaline elution technique was introduced which allows quantification of SSB together with base damage (SSB + BD). These methods have now been applied successfully to study the in vivo induction and repair of DNA damage in WBC of leukaemia patients who prior to BMT were treated with cyclophosphamide (CY) and received TBI. SSB and SSB + BD were determined after two treatments with CY (60 mg kg-1) followed by TBI (4.5-8.6Gy). The CY treatments gave rise to rather persistent SSB. In addition to these, radiation-induced SSB and SSB + BD could be detected shortly after TBI. However, 105 min after TBI, these SSB could be observed no longer, as a result of rapid repair.
Subject
Antineoplastic agent
Cyclophosphamide
Adult
Cancer chemotherapy
Cancer radiotherapy
Case report
DNA strand breakage
Human
Human cell
Intravenous drug administration
Leukemia
Leukocyte
Male
Priority journal
Acute Disease
Cyclophosphamide
DNA Damage
DNA, Single-Stranded
Human
Leukemia
Leukemia, Lymphocytic, Acute
Leukemia, Myeloid
Leukocytes
Lymphoma, Non-Hodgkin
Middle Age
Support, Non-U.S. Gov't
Whole-Body Irradiation
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TNO identifier
231753
ISSN
0020-7616
Source
International Journal of Radiation Biology, 62 (1), 33-43
Bibliographical note
Correspondence Address: Van Der Schans, G.P.; TNO Medical Biological Laboratory, PO Box 45, 2280 AA Rijswijk, Netherlands Chemicals/CAS: cyclophosphamide, 50-18-0; Cyclophosphamide, 50-18-0; DNA, Single-Stranded
Document type
article