The influence of bromodeoxyuridine on the induction and repair of DNA double-strand breaks in glioblastoma cells.
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.
Nusser
Nadine N
NN
Department of Human Genetics, University Hospital Ulm, Germany.
Bartkowiak
Detlef
D
Röttinger
Erwin M
EM
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
D003470:Culture Media; D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine