Radiosensitivity is predicted by DNA end-binding complex density, but not by nuclear levels of band components.

Background And Purpose: We previously determined that the density of a rapidly migrating DNA end-binding complex (termed 'band-A') predicts radiosensitivity of human normal and tumor cells. The goal of this study was first to identify the protein components of band-A and to determine if the protein levels of band-A components would correlate with band-A density and radiosensitivity.

Patients And Methods: DNA end-binding protein complex (DNA-EBC) protein components were identified by adding antibodies specific for a variety of DNA repair-associated proteins to the DNA-EBC reaction and then noting which antibodies super-shifted various DNA-EBC bands.

Accumulation of the common mitochondrial DNA deletion induced by ionizing radiation.

Point mutations and deletions in mitochondrial DNA (mtDNA) accumulate as a result of oxidative stress, including ionizing radiation. As a result, dysfunctional mitochondria suffer from a decline in oxidative phosphorylation and increased release of superoxides and other reactive oxygen species (ROS). Through this mechanism, mitochondria have been implicated in a host of degenerative diseases.

Predicting radiosensitivity using DNA end-binding complex analysis.

Previous reports have suggested that measuring radiosensitivity of normal and tumor cells would have significant clinical relevance for the practice of radiation oncology. We hypothesized that radiosensitivity might be predicted by analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand breaks, the most important cytotoxic lesion caused by radiation. To test this hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15 tumor cell lines were studied.

DNA-PK and ATM are required for radiation-enhanced integration.

Ionizing radiation is known to improve transfection of exogenous DNA, a process we have termed radiation-enhanced integration. Previous observations have demonstrated that Ku proteins are critical for radiation-enhanced integration. Since Ku proteins form the DNA-binding domain of DNA-PK and since DNA-PK is important in nonhomologous DNA end joining, it was hypothesized that DNA-PK function might be important for radiation-enhanced integration.