Tudek B, Swoboda M, Kowalczyk P, Oliński R
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
J Physiol Pharmacol. 2006 Nov;57 Suppl 7:33-49.
Oxidative DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important for the organism development as well as its pathogenesis, including cancer. Activity of DNA repair enzymes can depend on many factors, such as gene polymorphism, mRNA and protein level, as well as enzymes activation and inhibition. Modulation of base excision repair pathway eliminating from DNA oxidatively formed lesions may be caused by the diet, inflammation and neoplastic transformation. Reactive oxygen species and some diet components induce transcription of several Base Excision Repair enzymes, e.g. major human AP-endonuclease, (APE1) and 8-oxoG-DNA glycosylase (OGG1). The carcinogenic process in human lung decreases repair activity for 8-oxoGin transcription independent manner, but increases repair activity of epsilon A and epsilon C, as measured in tumors and unchanged lung tissues of lung cancer patients. Thus, modulation of repair enzymes activities may be a cell response on their way to differentiation ot neoplastic transformation.
氧化性DNA损伤和DNA修复可能介导多种细胞过程，如复制和转录、诱变和凋亡，因此可能对生物体发育及其发病机制（包括癌症）都很重要。DNA修复酶的活性可能取决于许多因素，如基因多态性、mRNA和蛋白质水平，以及酶的激活和抑制。饮食、炎症和肿瘤转化可能会调节碱基切除修复途径，以消除DNA中氧化形成的损伤。活性氧和一些饮食成分会诱导几种碱基切除修复酶的转录，例如主要的人类AP内切核酸酶（APE1）和8-氧代鸟嘌呤DNA糖基化酶（OGG1）。在肺癌患者的肿瘤和未改变的肺组织中检测发现，人类肺癌的致癌过程以转录独立的方式降低了对8-氧代鸟嘌呤的修复活性，但增加了εA和εC的修复活性。因此，修复酶活性的调节可能是细胞在分化或肿瘤转化过程中的一种反应。
