title: Residual DNA double strand breaks in perfused but not in unperfused areas determine different radiosensitivity of tumours.
abstract: OBJECTIVE
  Micromilieu-dependent quantification of γH2AX after irradiation in vivo and correlation with local tumour control.
  
  
  METHODS
  Local tumour control was evaluated after irradiation of FaDu and SKX xenografts with ambient single doses. γH2AX foci were quantified in perfused and unperfused regions after different irradiation doses and at different time points.
  
  
  RESULTS
  The TCD(50) of FaDu was 2-times higher compared to SKX (28.0Gy [95% C.I. 24.6; 31.3Gy] for FaDu; 14.9Gy [10.9; 18.9] for SKX, p<0.001). The induction of foci did not differ between the tumour models. Residual foci were twice higher in perfused SKX regions compared to FaDu, no difference was observed in the non-perfused region between both tumour models. The number of residual foci increased with a 2-times higher slope in perfused SKX-regions compared to FaDu, while no difference was detected in unperfused regions. Already within the perfused regions, this slope decreased with distance from perfused vessels.
  
  
  CONCLUSIONS
  The dose-response of residual γH2AX foci is highly dependent on tumour cell oxygenation in well perfused areas. This dependence decreases further away from tumour vessels. Only γH2AX evaluation in perfused tumour areas can distinguish between the different radiocurability of the two tumour models.
authors.affiliation: Department of Radiation Oncology, Technische Universität Dresden, Germany. mechthild.krause@uniklinikum-dresden.de
authors.forename: Apostolos
authors.initials: A
authors.lastname: Menegakis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eicheler
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D005260:Female; D006657:Histones / Q000032:analysis; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000098:blood supply / Q000235:genetics / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D011836:Radiation Tolerance
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse; D001973:Bromodeoxyuridine