Potential for the G2/M Arrest Assay to Predict Patient Susceptibility to Severe Reactions Following Radiotherapy Export

@article{citeulike:2860872, abstract = {Background and Purpose:\ \ Cell-cycle regulation and checkpoint activation are crucial factors for radiation-induced DNA damage processing. The G2/M phase arrest was assessed in lymphoblastoid cell lines and phytohemagglutinin-stimulated T-lymphocytes of different radiosensitivities to study the relationship of G2/M arrest to radiosensitivity.Material and Methods:\ \ G2/M arrest was analyzed after in vitro irradiation by 2 and 5 Gy of ionizing radiation up to 6 days using 17 lymphoblastoid cell lines from healthy individuals, ataxia-telangiectasia (AT) patients, Nijmegen breakage syndrome (NBS) patients and cancer patients with clinically increased radiosensitivity. In a second approach, phytohemagglutinin-stimulated T-lymphocytes from 15 healthy individuals, twelve cancer patients, and five cancer patients hypersensitive to ionizing radiation were studied. Image cytometry was performed to analyze G2/M arrest.Results:\ \ Two of the three AT cell lines showed markedly increased G2/M arrest compared to controls. NBS cells were comparable to controls up to day 3, but then demonstrated a slightly increased G2/M arrest. Two of the six radiosensitive lymphoblast cell lines and the five radiosensitive cancer patients' T-lymphocytes assayed showed a reduction in G2/M arrest, while healthy individuals showed no difference from cancer patients.Conclusion:\ \ The interrelation between G2/M arrest and radiosensitivity is not readily apparent since a variety of radiosensitive cells from patients with radiosensitive syndromes and patients identified as radiosensitive following radiation treatment showed inconsistent G2/M arrest dynamics. Secondary effects, like loss of clonogenicity, G1/S phase arrest and failure of G2/M arrest may contribute to variation of the G2/M arrest endpoint and obscure assessment of cellular radiosensitivity using this method.}, author = {Perez, Alexandra and Grabenbauer, Gerhard and Sprung, Carl and Sauer, Rolf and Distel, Luitpold}, citeulike-article-id = {2860872}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00066-007-1565-9}, day = {23}, doi = {10.1007/s00066-007-1565-9}, journal = {Strahlentherapie und Onkologie}, keywords = {cellcycle, facs, lymphoblastoids, lymphocytes}, month = {February}, number = {2}, pages = {99--106}, posted-at = {2008-06-04 13:23:38}, priority = {0}, title = {Potential for the G2/M Arrest Assay to Predict Patient Susceptibility to Severe Reactions Following Radiotherapy}, url = {http://dx.doi.org/10.1007/s00066-007-1565-9}, volume = {183}, year = {2007} }

TY - JOUR ID - citeulike:2860872 L3 - citeulike-article-id:2860872 N2 - Background and Purpose:  Cell-cycle regulation and checkpoint activation are crucial factors for radiation-induced DNA damage processing. The G2/M phase arrest was assessed in lymphoblastoid cell lines and phytohemagglutinin-stimulated T-lymphocytes of different radiosensitivities to study the relationship of G2/M arrest to radiosensitivity.Material and Methods:  G2/M arrest was analyzed after in vitro irradiation by 2 and 5 Gy of ionizing radiation up to 6 days using 17 lymphoblastoid cell lines from healthy individuals, ataxia-telangiectasia (AT) patients, Nijmegen breakage syndrome (NBS) patients and cancer patients with clinically increased radiosensitivity. In a second approach, phytohemagglutinin-stimulated T-lymphocytes from 15 healthy individuals, twelve cancer patients, and five cancer patients hypersensitive to ionizing radiation were studied. Image cytometry was performed to analyze G2/M arrest.Results:  Two of the three AT cell lines showed markedly increased G2/M arrest compared to controls. NBS cells were comparable to controls up to day 3, but then demonstrated a slightly increased G2/M arrest. Two of the six radiosensitive lymphoblast cell lines and the five radiosensitive cancer patients' T-lymphocytes assayed showed a reduction in G2/M arrest, while healthy individuals showed no difference from cancer patients.Conclusion:  The interrelation between G2/M arrest and radiosensitivity is not readily apparent since a variety of radiosensitive cells from patients with radiosensitive syndromes and patients identified as radiosensitive following radiation treatment showed inconsistent G2/M arrest dynamics. Secondary effects, like loss of clonogenicity, G1/S phase arrest and failure of G2/M arrest may contribute to variation of the G2/M arrest endpoint and obscure assessment of cellular radiosensitivity using this method. IS - 2 JF - Strahlentherapie und Onkologie EP - 106 TI - Potential for the G2/M Arrest Assay to Predict Patient Susceptibility to Severe Reactions Following Radiotherapy VL - 183 SP - 99 KW - cellcycle KW - facs KW - lymphoblastoids KW - lymphocytes AU - Perez, Alexandra AU - Grabenbauer, Gerhard AU - Sprung, Carl AU - Sauer, Rolf AU - Distel, Luitpold PY - 2007/02/23/ UR - http://dx.doi.org/10.1007/s00066-007-1565-9 ER -