Enhancement of Methyl Methanesulfonate-Induced Base Excision Repair in the Presence of Selenomethionine on p53-Dependent Pathway

• Published in: Journal of medicinal food Vol. 12; no. 2; pp. 340 - 344
• Main Authors: Jung, Hwa Jin, Lee, Ju Han, Seo, Young R
• Format: Journal Article
• Language: English
• Published: United States 01.04.2009
• Subjects: antioxidants; Antioxidants - pharmacology; biochemical pathways; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; chemical structure; chemoprevention; cultured cells; DNA damage; DNA Damage - drug effects; DNA Damage - genetics; DNA repair; DNA Repair - drug effects; DNA Repair - genetics; Gene Expression; gene expression regulation; genotoxicity; Humans; in vitro studies; methionine; methyl methanesulfonate; Methyl Methanesulfonate - adverse effects; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; oxidative stress; RNA, Small Interfering; selenium; selenomethionine; Selenomethionine - pharmacology; Transfection; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1096-620X; 1557-7600
• 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.