Cytotechnology. 1998 Sep;27(1-3):175-85. doi: 10.1023/A:1008064804678.
Most cytotoxic agents exert their action via damage of DNA. Therefore, the repair of such lesions is of major importance for the sensitivity of malignant cells to chemotherapeutic agents. The underlying mechanisms of various DNA repair pathways have extensively been studied in yeast, bacteria and mammalian cells. Sensitive and drug resistant cancer cell lines have provided models for analysis of the contribution of DNA repair to chemosensitivity. However, the validity of results obtained by laboratory experiments with regard to the clinical situation is limited. In both acute and chronic leukaemias, the emergence of drug resistant cells is a major cause for treatment failure. Recently, assays have become available to measure cellular DNA repair capacity in clinical specimens at the single-cell level. Application of these assays to isolated lymphocytes from patients with chronic lymphatic leukaemia (CLL) revealed large interindividual differences in DNA repair rates. Accelerated O(6)-ethylguanine elimination from DNA and faster processing of repair-induced single-strand breaks were found in CLL lymphocytes from patients nonresponsive to chemotherapy with alkylating agents compared to untreated or treated sensitive patients. Moreover, modulators of DNA repair with different target mechanisms were identified which also influence the sensitivity of cancer cells to alkylating agents. In this article, we review the current knowledge about the contribution of DNA repair to drug resistance in human leukaemia.
大多数细胞毒性药物通过破坏 DNA 发挥作用。因此，此类损伤的修复对于恶性细胞对化疗药物的敏感性至关重要。在酵母、细菌和哺乳动物细胞中，已广泛研究了各种 DNA 修复途径的潜在机制。敏感和耐药癌细胞系为分析 DNA 修复对化疗敏感性的贡献提供了模型。然而，实验室实验获得的结果与临床情况的相关性是有限的。在急性和慢性白血病中，耐药细胞的出现是治疗失败的主要原因。最近，已经有检测方法可用于在单细胞水平上测量临床标本中的细胞 DNA 修复能力。将这些检测方法应用于慢性淋巴细胞白血病 (CLL) 患者的分离淋巴细胞，结果显示 DNA 修复率存在很大的个体间差异。与未经治疗或治疗敏感的患者相比，对烷化剂化疗无反应的 CLL 淋巴细胞中 O(6)-乙基鸟嘌呤从 DNA 中的消除速度加快，并且修复诱导的单链断裂的处理速度更快。此外，还确定了具有不同靶机制的 DNA 修复调节剂，它们也会影响癌细胞对烷化剂的敏感性。本文综述了目前关于 DNA 修复对人类白血病耐药性的贡献的知识。
