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- W2116731507 abstract "Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53-wild type cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53-wild type RKO cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating cell nucleus antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B73." @default.
- W2116731507 created "2016-06-24" @default.
- W2116731507 creator A5017613692 @default.
- W2116731507 date "2011-10-01" @default.
- W2116731507 modified "2023-09-26" @default.
- W2116731507 title "Abstract B73: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair" @default.
- W2116731507 doi "https://doi.org/10.1158/1940-6207.prev-11-b73" @default.
- W2116731507 hasPublicationYear "2011" @default.
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