Clayson D B, Mehta R, Iverson F
Toxicology Research Division, National Health and Welfare, Ottawa, Ont., Canada.
Mutat Res. 1994 Feb;317(1):25-42. doi: 10.1016/0165-1110(94)90010-8.
A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect. Oxidative DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewed for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidative DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with aging are the result of the accumulation of lesions resulting from unrepaired oxidative DNA damage.
未经处理的人类和动物DNA中通常存在各种各样的氧化性DNA损伤。其中一种损伤，8-羟基脱氧鸟苷，已被证明会导致DNA复制时的碱基错配（突变）。其他损伤在这方面仍有待研究。在适当情况下，细胞复制时的氧化性DNA损伤可能会导致原癌基因激活。氧化性DNA损伤在固定时也可能导致细胞毒性，随后引发再生性增殖。本文综述了各类致癌物和自然过程中氧化性DNA损伤可能具有的重要性，包括金属离子、高能辐射、各种化学物质、肿瘤促进剂、多羟基酚/醌、脂质代谢、过氧化物酶体增殖剂和甲状腺功能。结论是，尽管在许多这些例子中证据需要大力加强，但现有信息表明氧化性DNA损伤在这些因素诱发肿瘤中具有潜在重要性。与衰老相关的非癌性退行性疾病也有可能是未修复的氧化性DNA损伤所导致的损伤积累的结果。
