Enhancement of methyl methanesulfonate-induced base excision repair in the presence of selenomethionine on p53-dependent pathway.
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.
Jung
Hwa Jin
HJ
Department of Pharmacology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Lee
Ju Han
JH
Seo
Young R
YR
D000975:Antioxidants / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008741:Methyl Methanesulfonate / Q000009:adverse effects; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D012645:Selenomethionine / Q000494:pharmacology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
D000975:Antioxidants; D018797:Cell Cycle Proteins; D008741:Methyl Methanesulfonate; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012645:Selenomethionine; D016159:Tumor Suppressor Protein p53; C439070:GADD45A protein, human; D000097642:GADD45 Proteins