A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse.
We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.
Okayasu
R
R
Department of Radiological Health Sciences, Colorado State University, Fort Collins 80523-1673, USA. rokayasu@cvmbs.colostate.edu
Suetomi
K
K
Yu
Y
Y
Silver
A
A
Bedford
J S
JS
Cox
R
R
Ullrich
R L
RL
D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D019281:Dimerization; D004198:Disease Susceptibility; D005260:Female; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects; D007700:Kinetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity
D004268:DNA-Binding Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases