The aim of our study was to determine the protective efficacy of the PrC-210 aminothiol radioprotector against X-ray-induced DNA damage in normal human cells and to establish dose- and time-effect models for future PrC-210 use in humans. The PrC-210 structure has a branched structure which enables scavenging of reactive oxygen species (ROS) away from DNA. Normal human blood lymphocytes, fibroblasts and naked genomic DNA were exposed to PrC-210 seconds to hours prior to irradiation. Biological (γ-H2AX foci), chemical (8-oxo-deoxyguanosine) and physical (genomic DNA electrophoretic migration) DNA damage endpoints were scored to determine the ability of PrC-210 to suppress radiation-induced DNA damage. X-ray-induced γ-H2AX foci in blood lymphocytes were reduced by 80% after irradiation with 10, 50 and 100 mGy, and DNA double-strand breaks in fibroblasts were reduced by 60% after irradiation with 20 Gy. Additionally, we observed a reduction of 8-oxo-deoxyguanosine (an ROS-mediated, DNA damage marker) in human genomic DNA to background in a PrC-210 dose-dependent manner. PrC-210 also eliminated radiation-induced cell death in colony formation assays after irradiation with 1 Gy. The protective efficacy of PrC-210 in each of these assay systems supports its development as a radioprotector for humans in multiple radiation exposure settings.

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an OH pulse reduced to background theOH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

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