Detection of single-strand breaks and base damage in DNA of blood cells from leukaemia patients receiving chemo- and radiotherapy
article
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.
Topics
Antineoplastic agentCyclophosphamideAdultCancer chemotherapyCancer radiotherapyCase reportDNA strand breakageHumanHuman cellIntravenous drug administrationLeukemiaLeukocyteMalePriority journalAcute DiseaseCyclophosphamideDNA DamageDNA, Single-StrandedHumanLeukemiaLeukemia, Lymphocytic, AcuteLeukemia, MyeloidLeukocytesLymphoma, Non-HodgkinMiddle AgeSupport, Non-U.S. Gov'tWhole-Body Irradiation
TNO Identifier
231753
ISSN
00207616
Source
International Journal of Radiation Biology, 62(1), pp. 33-43.
Pages
33-43
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