title: Overview of radiosensitivity of human tumor cells to low-dose-rate irradiation.
abstract: OBJECTIVE
  We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines.
  
  
  METHODS
  We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines.
  
  
  RESULTS
  Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses ( approximately 2 Gy HDR, approximately 6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours.
  
  
  CONCLUSIONS
  Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications.
authors.affiliation: Molecular Radiation Biology Program, Department of Radiation Medicine, Loma Linda Medical Center, Loma Linda, CA, USA.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Williams
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haoming
authors.initials: H
authors.lastname: Zhou
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Koch
authors.forename: James M
authors.initials: JM
authors.lastname: Slater
authors.forename: John B
authors.initials: JB
authors.lastname: Little
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009154:Mutation / Q000528:radiation effects; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000528:radiation effects