DNA strand breaks in human leukocytes induced by chemotherapy and total body irradiation.
The occurrence of DNA strand breaks and/or DNA alkali-labile sites in peripheral blood leucocytes was demonstrated ex vivo in three patients during and after bone marrow ablative chemotherapy and total body irradiation (TBI) with use of fluorometric analysis of the DNA unwinding rate in alkaline solution (FADU assay). DNA damage was apparent after cyclophosphamide administration and after TBI, related to the amount of the applied dose. In vivo repair occurred within 24 hours, although not to pretreatment values. Demethoxydaunorubicin and busulfan at the dosages used did not induce measurable DNA strand breaks. The experiences described may be developed further to study ex vivo the occurrence of DNA lesions in patients during and after anticancer treatment. Such studies may be of value in comparing the DNA damaging potential of different chemotherapeutic or radiotherapeutic regimens and as a biological assessment of DNA damage after nuclear casualties in cases where the dose is greater than 1-2 Gy and measurement can be made within due time after the ionizing exposure.
Franssen
C
C
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Boekema
P
P
De Witte
T
T
Wessels
J
J
Van der Kogel
A
A
Haanen
C
C
D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood / Q000235:genetics / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005470:Fluorometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics / Q000628:therapy; D007962:Leukocytes / Q000187:drug effects* / Q000528:radiation effects; D011879:Radiotherapy Dosage; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D004273:DNA, Neoplasm; D003520:Cyclophosphamide; D004247:DNA