Popanda Odilia, Ebbeler Reinhard, Twardella Dorothee, Helmbold Irmgard, Gotzes Florian, Schmezer Peter, Thielmann Heinz Walter, von Fournier Dietrich, Haase Wulf, Sautter-Bihl Marie Luise, Wenz Frederik, Bartsch Helmut, Chang-Claude Jenny
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1216-25. doi: 10.1016/s0360-3016(02)04415-2.
Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy.
Breast cancer patients receiving radiation therapy after a breast-conserving surgery were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryo-preserved lymphocytes from 113 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 26) of cells from a healthy donor. A coefficient of variation of 0.3 was calculated.
The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Eleven patients were identified with considerably enhanced DNA damage induction, and 7 patients exhibited severely reduced DNA repair capacity after 15 and 30 min. Six patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of about 50 Gy.
Using the alkaline comet assay as described here, breast cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin. Because impaired DNA repair could be involved in the development of late irradiation effects, individuals exhibiting severely reduced DNA repair capacity should be followed for the development of late clinical symptoms.
修复辐射诱导的DNA损伤对于患者放疗后发生副作用的易感性及其后续患癌风险均起着关键作用。本研究的目的是评估体外测定的DNA修复数据是否与放疗期间急性副作用的发生相关。
在一项前瞻性流行病学研究中招募了保乳手术后接受放射治疗的乳腺癌患者。记录皮肤不良反应作为临床放射敏感性指标。对113名研究参与者的冷冻保存淋巴细胞进行体外5 Gy的γ射线照射，并使用碱性彗星试验进行分析。通过对健康供体的细胞进行重复分析（n = 26）来确定该试验的可重复性。计算出变异系数为0.3。
为表征个体DNA修复能力而测定的各种参数在患者之间显示出很大差异。11名患者被确定为DNA损伤诱导显著增强，7名患者在15分钟和30分钟后显示出DNA修复能力严重降低。6名患者被认为具有临床放射敏感性，表现为在总辐射剂量约50 Gy后皮肤出现湿性脱屑。
使用本文所述的碱性彗星试验，鉴定出乳腺癌患者存在异常的细胞辐射效应，但这种修复缺陷仅在非常有限的程度上与皮肤的急性辐射敏感性相关。由于DNA修复受损可能与晚期辐射效应的发生有关，因此应对DNA修复能力严重降低的个体进行随访，观察晚期临床症状的发展。
