Kopnin B P
Mol Biol (Mosk). 2007 Mar-Apr;41(2):369-80.
Molecular alterations leading to genetic instability play a key role in tumor development. The basic reasons of genetic instability of tumor cells, i.e. up-regulation of intracellular level of endogenous mutagens, in particular reactive oxygen spesies (ROS); decreased fidelity of DNA replication and chromosome segregation in mitosis; defects in DNA repair systems; and inactivation of cell cycle checkpoints preventing proliferation of abnormal cells are reviewed. In addition, tissue-specificity of tumorigenesis connected with genetic instability and development of new therapeutic approaches based on diminishing genetic instability or selective killing of neoplastic cells showing such defects are discussed.
导致基因不稳定的分子改变在肿瘤发展中起关键作用。本文综述了肿瘤细胞基因不稳定的基本原因，即内源性诱变剂（特别是活性氧物种（ROS））细胞内水平上调；有丝分裂中DNA复制保真度降低和染色体分离异常；DNA修复系统缺陷；以及防止异常细胞增殖的细胞周期检查点失活。此外，还讨论了与基因不稳定相关的肿瘤发生组织特异性，以及基于减少基因不稳定或选择性杀死显示此类缺陷的肿瘤细胞而开发的新治疗方法。
