Smith M L, Fornace A J
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892, USA.
Mutat Res. 1996 Jun;340(2-3):109-24. doi: 10.1016/s0165-1110(96)90043-3.
Mammalian cells are exposed to a wide variety of genotoxic stresses from both endogenous and exogenous sources. Cells typically exhibit cell cycle delays, or checkpoints, in response to acute genotoxic stress. Other types of cellular responses to DNA damage include apoptosis and probably increases in DNA repair levels. These response pathways are altered in cancer cells, by genetic alterations such as overexpression or mutation of oncogenes, or loss of tumor suppressor gene functions. As cancer chemotherapy relies primarily on the selective killing of cancer cells by DNA-damaging agents, genetic alterations affecting cellular stress response pathways may affect the outcome of cancer treatment.
哺乳动物细胞会受到来自内源性和外源性多种基因毒性应激的影响。细胞通常会对急性基因毒性应激作出反应，表现为细胞周期延迟或检查点。细胞对DNA损伤的其他类型反应包括细胞凋亡，DNA修复水平可能也会提高。这些反应途径在癌细胞中会因基因改变而发生变化，比如癌基因的过表达或突变等遗传改变，或者肿瘤抑制基因功能的丧失。由于癌症化疗主要依赖于通过DNA损伤剂选择性杀死癌细胞，影响细胞应激反应途径的基因改变可能会影响癌症治疗的结果。
