title: The influence of bromodeoxyuridine on the induction and repair of DNA double-strand breaks in glioblastoma cells.
abstract: OBJECTIVE
  To examine the dose response of DNA damage and its modification by the radiosensitizer, 5-bromo-2'-deoxyuridine (BrdU). The sensitizing mechanism is analyzed with regard to its influence on the induction and repair of DNA double-strand breaks (DSBs).
  
  
  METHODS
  Cells from three different human glioblastoma lines, A7, LH and U87MG, were X-irradiated with and without exposure to BrdU. DNA fragments were separated by field-inversion gel electrophoresis (FIGE) and quantified by fluorometry immediately and 24 h after irradiation.
  
  
  RESULTS
  In all cell lines, the dose response followed a linear-quadratic rather than a purely linear function. BrdU-treated cells exhibited a significantly higher amount of mobile DNA. In repair experiments with and without BrdU, the amount of mobile DNA fell close to control values within 24 h.
  
  
  CONCLUSIONS
  The linear-quadratic model appropriately describes the X-ray-induced fragmentation of DNA. BrdU sensitizing acts predominantly by increasing DNA fragility, and not by impairing damage repair. The amount of DSBs persistent after 24 h of repair is minimal, even after highly cytotoxic doses. However, it appears to depend on the extent of initial damage, causing sensitized cells to retain more DSBs than unsensitized cells.
authors.affiliation: Department of Human Genetics, University Hospital Ulm, Germany.
authors.forename: Nadine N
authors.initials: NN
authors.lastname: Nusser
authors.forename: Detlef
authors.initials: D
authors.lastname: Bartkowiak
authors.forename: Erwin M
authors.initials: EM
authors.lastname: Röttinger
mesh_terms: D001973:Bromodeoxyuridine / Q000494:pharmacology*; D003470:Culture Media; D004249:DNA Damage / Q000528:radiation effects; D053938:DNA Fragmentation; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D016521:Electrophoresis, Gel, Pulsed-Field; D005470:Fluorometry; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
chemical_list: D003470:Culture Media; D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine