Jung Hwa Jin, Lee Ju Han, Seo Young R
Department of Pharmacology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
J Med Food. 2009 Apr;12(2):340-4. doi: 10.1089/jmf.2007.0709.
Selenomethionine (SeMet) has been identified as a chemopreventive antioxidant to activate p53-mediated nucleotide excision repair. In this study, we examined whether p53-mediated base excision repair (BER) might be induced by SeMet. When methyl methanesulfonate, a BER-inducing agent, was treated in the cells, DNA damage was rapidly decreased in the presence of SeMet. In addition, our data showed that the removal of apurinic/apyrimidinic sites was significantly enhanced in the presence of SeMet. Furthermore, we observed that the expression of gadd45a, known to involve BER as one of the p53 downstream genes, was increased by SeMet in p53 wild-type RKO cells. Those results supported the proposal that BER activity might be dependent on wild-type p53 under the modulation of gadd45a expression in response to SeMet. We suggested that p53-dependent BER activity as a distinct mechanism of SeMet might play an important role to prevent cancer caused by various oxidative stresses.
硒代蛋氨酸（SeMet）已被确定为一种化学预防抗氧化剂，可激活p53介导的核苷酸切除修复。在本研究中，我们检测了SeMet是否可能诱导p53介导的碱基切除修复（BER）。当用甲基磺酸甲酯（一种BER诱导剂）处理细胞时，在有SeMet存在的情况下，DNA损伤迅速减少。此外，我们的数据表明，在有SeMet存在的情况下，无嘌呤/无嘧啶位点的去除显著增强。此外，我们观察到，在p53野生型RKO细胞中，SeMet可增加gadd45a的表达，gadd45a作为p53下游基因之一，已知参与BER。这些结果支持了这样的观点，即在gadd45a表达的调节下，BER活性可能依赖于野生型p53以响应SeMet。我们认为，p53依赖的BER活性作为SeMet的一种独特机制，可能在预防由各种氧化应激引起的癌症中发挥重要作用。
