Franssen C, Boekema P, De Witte T, Wessels J, Van der Kogel A, Haanen C
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Leuk Res. 1990;14(1):91-7. doi: 10.1016/0145-2126(90)90151-x.
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.
通过碱性溶液中DNA解旋速率的荧光分析(FADU测定法),在体外证实了三名患者在骨髓清除性化疗和全身照射(TBI)期间及之后外周血白细胞中DNA链断裂和/或DNA碱不稳定位点的出现。环磷酰胺给药后及TBI后,DNA损伤明显,且与所给予剂量的大小有关。体内修复在24小时内发生,尽管未恢复到预处理值。所用剂量的去甲氧基柔红霉素和白消安未诱导可测量的DNA链断裂。所描述的这些经验可进一步拓展,以在体外研究抗癌治疗期间及之后患者体内DNA损伤的发生情况。此类研究在比较不同化疗或放疗方案的DNA损伤潜力方面可能具有价值,并且在剂量大于1 - 2 Gy且在电离照射后适当时间内可进行测量的情况下,作为核事故后DNA损伤的生物学评估也具有价值。