Protective effects of selenomethionine against ionizing radiation under the modulation of p53 tumor suppressor.
Ionizing radiation (IR) therapy has been widely employed in the treatment of cancer. However, certain issues, including toxicity, have been raised in conjunction with IR therapy for cancer. Recently, selenomethionine (SeMet) as an antioxidant has been the subject of a great deal of attention for its chemopreventive effects. In this study, we found that DNA repair activity has been enhanced in response to SeMet against IR. In addition, our data showed that p53 functional activity was significantly reduced against IR in the cells expressing a mutant form of redox factor 1 (Ref-1) contrast with Ref-1 wild-type cells treated with SeMet, suggesting that p53 activation under the modulation of Ref-1 might play an important role in IR-treated cells in the presence of SeMet. Furthermore, IR-induced micronuclei numbers were also reduced after treatment with SeMet, strongly implicating protection by SeMet in genomic stability against IR-induced genotoxicity. From this study, we suggest that the p53-mediated protective mechanism of SeMet might provide clues for reducing side effects of IR therapy.
Jeong
Seok Won
SW
Department of Pharmacology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Jung
Hwa Jin
HJ
Rahman
Md Mujibur
MM
Hwang
Jee Na
JN
Seo
Young R
YR
D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D015870:Gene Expression; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D009154:Mutation; D011839:Radiation, Ionizing; D012645:Selenomethionine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000975:Antioxidants; D016159:Tumor Suppressor Protein p53; D004247:DNA; D012645:Selenomethionine; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase