A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse

• Published in: Cancer research (Chicago, Ill.) Ill.), 2000-08, Vol.60 (16), p.4342-4345
• Main Authors: Okayasu, R., Suetomi, K., Yu, Y., Silver, A., Bedford, J. S., Cox, R., Ullrich, R. L.
• Format: Article
• Language: English
• Subjects: Aerospace Medicine; Animals; Biological and medical sciences; Blotting, Western; Catalysis; Cells, Cultured; Dimerization; Disease Susceptibility; DNA - metabolism; DNA Damage; DNA Repair - physiology; DNA-Activated Protein Kinase; DNA-Binding Proteins; DNA-dependent protein kinase; Female; Fundamental and applied biological sciences. Psychology; Kidney - enzymology; Kidney - metabolism; Kidney - radiation effects; Kinetics; Male; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, SCID; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - metabolism; Radiation Tolerance - genetics; Radiation Tolerance - physiology; Space life sciences; Species Specificity
• ISSN: 0008-5472; 1538-7445

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.