title: Determinates of tumor response to radiation: tumor cells, tumor stroma and permanent local control.
abstract: OBJECTIVE
  The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose.
  
  
  METHODS
  Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs(-/-)) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD50 assay. Vascular effects were evaluated by functional vascular density assays.
  
  
  RESULTS
  The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses.
  
  
  CONCLUSIONS
  The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA; Guangdong Medical College, PR China.
authors.forename: Wende
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA.
authors.forename: Peigen
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA. Electronic address: LGerweck@mgh.harvard.edu.
authors.forename: Leo E
authors.initials: LE
authors.lastname: Gerweck
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D007928:Lethal Dose 50; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D017154:Stromal Cells / Q000528:radiation effects; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D051747:DNA-Activated Protein Kinase
keywords: Intrinsic radiosensitivity; Predictive assays; Radiation; Tumor control dose; Tumor vasculature