Vodicka Pavel, Vodenkova Sona, Opattova Alena, Vodickova Ludmila
Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, 1083, 142 20, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 323 00, Pilsen, Czech Republic.
Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, 1083, 142 20, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00, Prague, Czech Republic; Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruska 2411/87, 100 00, Prague, Czech Republic.
Mutat Res Genet Toxicol Environ Mutagen. 2019 Jul;843:95-110. doi: 10.1016/j.mrgentox.2019.05.009. Epub 2019 May 20.
The last decade witnessed an increase in the use of comet assay for DNA damage monitoring in cancer patients and controls. Apart from case-control studies, reports described the determination of DNA damage prior to (baseline value) and after chemo-/radiotherapy, the treatment resulted in significantly elevated DNA damage. However, studies on DNA damage as a factor reflecting cancer prognosis and therapy prediction are scarce. In most cases, DNA damage was analysed in surrogate tissues. The data on DNA damage are available for 17 types of cancer. The reviewed data unambiguously pinpoint the usefulness of the comet assay in human cancer research due to its sensitivity and cost-effectiveness in evaluating DNA damage associated with the disease and with the treatment. DNA repair capacity (DRC) represents a complex marker for functional evaluation of multigene DNA repair processes in cancer onset with future prospects in personalized prevention and/or cancer treatment. A comparison between studies and more general conclusions are precluded by a variable design of the studies and a lack of standard protocol for both DNA damage and DRC determination. Since cancer is a heterogeneous complex disease, numerous points have to be considered: a) DNA damage and DRC measured in surrogate/target tissues, b) changes in the levels of DNA damage and DRC may be a cause or a consequence of the disease, c) changes in DRC alter sensitivity of tumour cells to antineoplastic drugs, d) one time point-sampling of patients provides insufficient information on the role of DNA damage and its repair in carcinogenesis. Finally, systemic cancer therapy is targeted at DNA damage and its repair. A proper understanding of these processes is a key precondition for the optimisation of therapy regimens, prediction of therapeutic response and prognosis in cancer patients.
在过去十年中，彗星试验在癌症患者和对照人群中用于监测DNA损伤的应用有所增加。除了病例对照研究外，还有报告描述了在化疗/放疗之前（基线值）和之后对DNA损伤的测定，结果显示治疗后DNA损伤显著升高。然而，将DNA损伤作为反映癌症预后和治疗预测因素的研究却很少。在大多数情况下，DNA损伤是在替代组织中进行分析的。目前已有17种癌症的DNA损伤数据。综述的数据明确指出彗星试验在人类癌症研究中的有用性，因为它在评估与疾病及治疗相关的DNA损伤方面具有敏感性和成本效益。DNA修复能力（DRC）是一个复杂的标志物，用于评估癌症发生过程中多基因DNA修复过程的功能，在个性化预防和/或癌症治疗方面具有未来前景。由于研究设计的多样性以及缺乏DNA损伤和DRC测定的标准方案，难以对各项研究进行比较并得出更普遍的结论。由于癌症是一种异质性复杂疾病，必须考虑众多要点：a）在替代/靶组织中测量的DNA损伤和DRC；b）DNA损伤和DRC水平的变化可能是疾病的原因或结果；c）DRC的变化会改变肿瘤细胞对抗肿瘤药物的敏感性；d）对患者进行一次性时间点采样，对于DNA损伤及其修复在致癌过程中的作用提供的信息不足。最后，全身性癌症治疗针对的是DNA损伤及其修复。正确理解这些过程是优化治疗方案、预测癌症患者治疗反应和预后的关键前提。
