title: Evidence for the expression of radiation-induced potentially lethal damage being a p53-dependent process.
abstract: OBJECTIVE
  To test the hypothesis that the expression of potentially lethal damage (PLD) is a p53-dependent process.
  
  
  METHODS
  Previously reported data on radiation sensitivity, DNA double-strand break rejoining, PLD expression and repair (PLDR) were analyzed for a group of 12 human tumor cell lines and three human diploid fibroblast cell lines. Seven of these cell lines had normal p53 gene expression while the other eight were functionally p53-deficient. None of the cell lines was sensitive to radiation-induced apoptosis.
  
  
  RESULTS
  Cell lines with a normal p53 expression were more sensitive to radiation, but only when sensitivity was measured in plateau-phase cultures under conditions where PLDR was minimized. Mutation or functional inactivation of p53 by HPV E6-transformation led to a more radioresistant phenotype under these conditions as well as a significant reduction in PLDR. PLDR was inversely proportional to the percentage of radiation-induced DNA double-strand breaks rejoined in 1 h in the p53 normal cell lines.
  
  
  CONCLUSIONS
  These results suggest that the expression of PLD is primarily a p53-dependent process. In the absence of functional p53 gene expression, the effects of PLD are minimized. These observations help clarify the role of p53 in tumor response to radiation therapy because they suggest that the effects of alterations in p53 are highly dependent on the microenvironment of the tumor, i.e. whether conditions allow for PLDR.
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle 98195, USA. jschawart@u.washington.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Schwartz
authors.forename: R
authors.initials: R
authors.lastname: Jordan
authors.forename: W K
authors.initials: WK
authors.lastname: Kaufmann
authors.forename: J
authors.initials: J
authors.lastname: Rasey
authors.forename: K J
authors.initials: KJ
authors.lastname: Russell
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D009154:Mutation