title: Effect of pH on radiation-induced p53 expression.
abstract: OBJECTIVE
  In most tumors, the intratumor environment is acidic. The purpose of this study was to elucidate the effect of acidic extracellular environment on the radiation-induced expression of p53 and related molecular signals.
  
  
  METHODS
  Cultured RKO.C human colorectal cancer cells carrying wild-type p53 were used. Cells grown in pH 7.5 medium or pH 6.6 medium were irradiated with gamma-rays, and the expression of p53 and p53 mRNA, as well as the degradation rate of the molecules, was determined. The transcriptional activity for p53 was investigated using cells transfected with a p53 reporter construct. The expression of Mdm2 and the phosphorylation of p53, essential factors for p53 degradation, were also investigated.
  
  
  RESULTS
  The pH 6.6 environment prolonged the radiation-induced expression of p53 and p53 mRNA. The radiation-induced increase in transcriptional activity of p53 lasted longer in pH 6.6 medium than in pH 7.5 medium. The degradation of p53 was delayed at pH 6.6. The radiation-induced expression of Mdm2 was markedly suppressed, whereas the phosphorylation of p53 was markedly increased after irradiation in pH 6.6 medium.
  
  
  CONCLUSIONS
  Acidic environment significantly enhances the radiation-induced expression of p53, partly by increasing the formation of p53 and also partly by slowing down the degradation of p53 through inhibiting p53-Mdm2 complex formation. The potential implication of acidic intratumor microenvironment for the response of tumors to radiotherapy remains to be elucidated.
authors.affiliation: Department of Therapeutic Radiology, College of Medicine, University of Ulsan, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Roberts
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: Taehee
authors.initials: T
authors.lastname: Han
authors.forename: Heon-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Song
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
mesh_terms: D045744:Cell Line, Tumor / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D003470:Culture Media; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53