title: The scid defect results in much slower repair of DNA double-strand breaks but not high levels of residual breaks.
abstract: Severe combined immune deficiency (scid) mice fail to produce mature B and T cells and are sensitive to ionizing radiation. They contain a mutation in the 460-kDa catalytic subunit of the DNA-dependent protein kinase that is involved in both V(D)J rejoining and DNA double-strand break (DSB) repair. The kinetics of DSB rejoining was quantified in both scid cells and the parental C.B-17 cells after three different doses of X irradiation: 3, 7.5 and 10 Gy. Repair of DNA DSBs was determined using pulsed-field gel electrophoresis, Southern hybridization and phosphor image analysis. After X irradiation, the cells were allowed to repair at 37 degrees C for up to 1 h or up to 24 h. The most profound difference between the two cell lines was the greatly reduced rate of the slow component of DSB repair in scid cells. C.B-17 cells repaired most of the damage within 1 h, whereas scid cells required 4 to 6 h to reach a similar level after the same dose. No residual or unrepairable DSBs were detected in either cell line 24 h after doses as high as 10 Gy. The scid cells subjected to two doses of 1.5 Gy separated by increasing amounts of time showed no ability to repair sublethal damage between doses, whereas C.B-17 cells receiving two doses of 3.75 Gy separated by increasing periods did show increased levels of survival. These results indicate that scid cells can repair radiation-induced DNA DSBs, although at a reduced rate, but they lack the ability to undergo repair of sublethal damage.
authors.affiliation: Department of Radiation Oncology, State University of New York Health Science Center, Syracuse 13210, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nevaldine
authors.forename: J A
authors.initials: JA
authors.lastname: Longo
authors.forename: P J
authors.initials: PJ
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D016513:Mice, SCID / Q000235:genetics*; D014965:X-Rays