ABSTRACT
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: M.B., M.S., W.E.F., M.U.; Methodology: M.B., M.S., F.J., W.E.F., M.U.; Software: W.E.F.; Validation: M.B., F.J., W.E.F., M.U.; Formal analysis: M.B., F.J., M.U.; Investigation: M.B., M.S., W.E.F., M.U.; Resources: M.B.; Data curation: M.S., F.J., W.E.F.; Writing - original draft: M.B., F.J., W.E.F., M.U.; Visualization: M.S.
Funding
A portion of this work was funded by grant number [R03 CA176799] CA/NCI National Institutes of Health HHS/United States to W.E.F.
- Received April 22, 2018.
- Accepted August 16, 2018.
- © 2018. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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