Repair of DNA Damage Induced by Accelerated Heavy Ions in Mammalian Cells Proficient and Deficient in the Non-homologous End-Joining Pathway Export

@article{citeulike:2518976, abstract = {Human and rodent cells proficient and deficient in non-homologous end joining (NHEJ) were irradiated with X rays, 70 keV/μm carbon ions, and 200 keV/μm iron ions, and the biological effects on these cells were compared. For wild-type CHO and normal human fibroblast (HFL III) cells, exposure to iron ions yielded the lowest cell survival, followed by carbon ions and then X rays. NHEJ-deficient xrs6 (a Ku80 mutant of CHO) and 180BR human fibroblast (DNA ligase IV mutant) cells showed similar cell survival for X and carbon-ion irradiation (RBE = ∼1.0). This phenotype is likely to result from a defective NHEJ protein because xrs6-hamKu80 cells (xrs6 cells corrected with the wild-type KU80 gene) exhibited the wild-type response. At doses higher than 1 Gy, NHEJ-defective cells showed a lower level of survival with iron ions than with carbon ions or X rays, possibly due to inactivation of a radioresistant subpopulation. The G1 premature chromosome condensation (PCC) assay with HFL III cells revealed LET-dependent impairment of repair of chromosome breaks. Additionally, iron-ion radiation induced non-repairable chromosome breaks not observed with carbon ions or X rays. PCC studies with 180BR cells indicated that the repair kinetics after exposure to carbon and iron ions behaved similarly for the first 6 h, but after 24 h the curve for carbon ions approached that for X rays, while the curve for iron ions remained high. These chromosome data reflect the existence of a slow NHEJ repair phase and severe biological damage induced by iron ions. The auto-phosphorylation of DNA-dependent protein kinase catalytic subunits (DNA-PKcs), an essential NHEJ step, was delayed significantly by high-LET carbon- and iron-ion radiation compared to X rays. This delay was further emphasized in NHEJ-defective 180BR cells. Our results indicate that high-LET radiation induces complex DNA damage that is not easily repaired or is not repaired by NHEJ even at low radiation doses such as 2 Gy.}, author = {Okayasu, Ryuichi and Okada, Maki and Okabe, Atsushi and Noguchi, Miho and Takakura, Kaoru and Takahashi, Sentaro}, citeulike-article-id = {2518976}, citeulike-linkout-0 = {http://www.bioone.org/perlserv/?request=get-abstract&issn=0033-7587&volume=165&page=59}, journal = {Radiation Research}, keywords = {fusionpcc, highlet}, month = {January}, number = {1}, pages = {59--67}, posted-at = {2008-03-12 09:31:07}, priority = {3}, title = {Repair of DNA Damage Induced by Accelerated Heavy Ions in Mammalian Cells Proficient and Deficient in the Non-homologous End-Joining Pathway}, url = {http://www.bioone.org/perlserv/?request=get-abstract&issn=0033-7587&volume=165&page=59}, volume = {165}, year = {2006} }

TY - JOUR ID - citeulike:2518976 L3 - citeulike-article-id:2518976 N2 - Human and rodent cells proficient and deficient in non-homologous end joining (NHEJ) were irradiated with X rays, 70 keV/μm carbon ions, and 200 keV/μm iron ions, and the biological effects on these cells were compared. For wild-type CHO and normal human fibroblast (HFL III) cells, exposure to iron ions yielded the lowest cell survival, followed by carbon ions and then X rays. NHEJ-deficient xrs6 (a Ku80 mutant of CHO) and 180BR human fibroblast (DNA ligase IV mutant) cells showed similar cell survival for X and carbon-ion irradiation (RBE = ∼1.0). This phenotype is likely to result from a defective NHEJ protein because xrs6-hamKu80 cells (xrs6 cells corrected with the wild-type KU80 gene) exhibited the wild-type response. At doses higher than 1 Gy, NHEJ-defective cells showed a lower level of survival with iron ions than with carbon ions or X rays, possibly due to inactivation of a radioresistant subpopulation. The G1 premature chromosome condensation (PCC) assay with HFL III cells revealed LET-dependent impairment of repair of chromosome breaks. Additionally, iron-ion radiation induced non-repairable chromosome breaks not observed with carbon ions or X rays. PCC studies with 180BR cells indicated that the repair kinetics after exposure to carbon and iron ions behaved similarly for the first 6 h, but after 24 h the curve for carbon ions approached that for X rays, while the curve for iron ions remained high. These chromosome data reflect the existence of a slow NHEJ repair phase and severe biological damage induced by iron ions. The auto-phosphorylation of DNA-dependent protein kinase catalytic subunits (DNA-PKcs), an essential NHEJ step, was delayed significantly by high-LET carbon- and iron-ion radiation compared to X rays. This delay was further emphasized in NHEJ-defective 180BR cells. Our results indicate that high-LET radiation induces complex DNA damage that is not easily repaired or is not repaired by NHEJ even at low radiation doses such as 2 Gy. IS - 1 JF - Radiation Research EP - 67 TI - Repair of DNA Damage Induced by Accelerated Heavy Ions in Mammalian Cells Proficient and Deficient in the Non-homologous End-Joining Pathway VL - 165 SP - 59 KW - fusionpcc KW - highlet AU - Okayasu, Ryuichi AU - Okada, Maki AU - Okabe, Atsushi AU - Noguchi, Miho AU - Takakura, Kaoru AU - Takahashi, Sentaro PY - 2006/01// UR - http://www.bioone.org/perlserv/?request=get-abstract&issn=0033-7587&volume=165&page=59 ER -