Tudek Barbara
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-75. doi: 10.1016/j.mam.2007.05.003. Epub 2007 Jun 2.
Oxidative DNA damage and DNA repair mediate the development of several human pathologies, including cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Functional assays performed in blood leukocytes of cancer patients and matched controls show that specific BER pathways are decreased in cancer patients, and may be risk factors. These include 8-oxoguanine (8-oxoG) repair in lung and head and neck cancer patients and repair of lipid peroxidation (LPO) induced 1,N(6)-ethenoadenine (epsilonA) in lung cancer patients. Decrease of excision of LPO-induced DNA damage, epsilonA and 3,N(4)-ethenocytosine (epsilonC) was observed in blood leukocytes of patients developing lung adenocarcinoma, specific histological type of cancer related to inflammation and healing of scars. BER proteins activity depends on gene polymorphism, interactions between BER system partners and post-translational modifications. Polymorphisms of DNA glycosylases may change their enzymatic activities, and some polymorphisms increase the risk of inflammation-related cancers, colorectal, lung and other types. Polymorphisms of BER platform protein, XRCC1 are connected with increased risk of tobacco-related cancers. BER efficiency may also be changed by reactive oxygen species and some diet components, which induce transcription of several glycosylases as well as a major human AP-endonuclease, APE1. BER is also changed in tumors in comparison to unaffected surrounding tissues, and this change may be due to transcription stimulation, post-translational modification of BER enzymes as well as protein-protein interactions. Modulation of BER enzymes activities may be, then, an important factor determining the risk of cancer and also may participate in cancer development.
氧化DNA损伤和DNA修复介导了包括癌症在内的多种人类疾病的发展。氧化DNA损伤修复的主要途径是碱基切除修复（BER）。在癌症患者和匹配的对照者的血液白细胞中进行的功能测定表明，癌症患者中特定的BER途径减少，可能是危险因素。这些包括肺癌、头颈癌患者中的8-氧鸟嘌呤（8-oxoG）修复以及肺癌患者中脂质过氧化（LPO）诱导的1,N(6)-乙烯腺嘌呤（εA）的修复。在发生肺腺癌（一种与炎症和疤痕愈合相关的特定组织学类型的癌症）的患者的血液白细胞中，观察到LPO诱导的DNA损伤、εA和3,N(4)-乙烯胞嘧啶（εC）的切除减少。BER蛋白的活性取决于基因多态性、BER系统伙伴之间的相互作用以及翻译后修饰。DNA糖基化酶的多态性可能会改变其酶活性，一些多态性会增加与炎症相关的癌症、结直肠癌、肺癌和其他类型癌症的风险。BER平台蛋白XRCC1的多态性与烟草相关癌症的风险增加有关。BER效率也可能受到活性氧和一些饮食成分的影响，这些成分会诱导几种糖基化酶以及主要的人类AP内切核酸酶APE1的转录。与未受影响的周围组织相比，肿瘤中的BER也会发生变化，这种变化可能是由于转录刺激、BER酶的翻译后修饰以及蛋白质-蛋白质相互作用。因此，调节BER酶的活性可能是决定癌症风险的一个重要因素，也可能参与癌症的发展。
