DNA Double-Strand Break Induction and Repair in Irradiated Lymphoblastoid, Fibroblast Cell Lines and White Blood Cells from ATM, NBS and Radiosensitive Patients.

Strasser, Hans; Grabenbauer, Gerhard; Sprung, Carl; Sauer, Rolf; Distel, Luitpold

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. LCLs from six healthy donors, seven patients with a heterozygous or homozygous genotype for ataxiatelangiectasia (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. 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. 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.

RADIATION carcinogenesis; ALLERGIES; LYMPHOBLASTOID cell lines; LEUKOCYTES; CANCER patients; GENETIC polymorphisms; BIOCHEMICAL genetics

Strahlentherapie und Onkologie, 2007, Vol 183, Issue 8, p447

0179-7158

Academic Journal

10.1007/s00066-007-1683-4