DNA double-strand break induction and repair in irradiated lymphoblastoid, fibroblast cell lines and white blood cells from ATM, NBS and radiosensitive patients.
OBJECTIVE
DNA double-strand breaks (dsbs) in lymphoblastoid cell lines (LCLs), fibroblasts and white blood cells from healthy donors, cancer patients with and without late effects of grade 3-4 (RTOG) as well as donors with known radiosensitivity syndromes were examined with the aim to detect dsb repair ability as a marker for radiosensitivity.


METHODS
LCLs from six healthy donors, seven patients with a heterozygous or homozygous genotype for ataxia-telangiectasia (ATM) and Nijmegen breakage syndrome (NBS), two patients with a late toxicity of grade 3-4 (RTOG), and one cell line with a ligase IV-/- status and its parental cell line were examined. Furthermore, fibroblasts from patients with ATM, NBS, two healthy control individuals, and leukocytes from 16 healthy and 22 cancer patients including seven patients with clinical hypersensitivity grade 3 (RTOG) were examined. Cells were irradiated in vitro with 0-150 Gy. Initial damage as well as remaining damage after 8 and 24 h were measured using constant field gel electrophoresis.


RESULTS
In contrast to cells derived from patients homozygous for NBS, impaired dsb repair ability could be detected both in fibroblast and lymphoblastoid cells from ATM and ligase IV-/- patients. The dsb repair ability of all 38 leukocyte cell lines (patients with grade 3-4 late effects and controls) was similar, whereas the initial damage among healthy donors was less.


CONCLUSIONS
Despite showing a clinically elevated radiosensitivity after irradiation, the DNA repair of the patients with clinical hypersensitivity grade 3 (RTOG) appeared to be normal. Other mechanisms such as mutations, altered cell cycle or defective apoptosis could play a critical role toward determining radiosensitivity.
Department of Radiation Oncology, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Hans
H
Strasser
Gerhard G
GG
Grabenbauer
Carl N
CN
Sprung
Rolf
R
Sauer
Luitpold V R
LV
Distel
D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000503:physiopathology; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D007962:Leukocytes / Q000528:radiation effects*; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D049932:Nijmegen Breakage Syndrome / Q000235:genetics* / Q000503:physiopathology; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics