Reduction of X-ray-induced DNA damage in normal human cells treated with the PrC-210 radioprotector

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Abstract

Summary: A new strategy is decribed, using a new radioprotector (PrC-210) to significantly reduce radiation-induced DNA damage.

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses.

K. Rothkamm, M Löbrich (2003)

DNA double-strand breaks (DSBs) are generally accepted to be the most biologically significant lesion by which ionizing radiation causes cancer and hereditary disease. However, no information on the induction and processing of DSBs after physiologically relevant radiation doses is available. Many of the methods used to measure DSB repair inadvertently introduce this form of damage as part of the methodology, and hence are limited in their sensitivity. Here we present evidence that foci of gamma-H2AX (a phosphorylated histone), detected by immunofluorescence, are quantitatively the same as DSBs and are capable of quantifying the repair of individual DSBs. This finding allows the investigation of DSB repair after radiation doses as low as 1 mGy, an improvement by several orders of magnitude over current methods. Surprisingly, DSBs induced in cultures of nondividing primary human fibroblasts by very low radiation doses (approximately 1 mGy) remain unrepaired for many days, in strong contrast to efficient DSB repair that is observed at higher doses. However, the level of DSBs in irradiated cultures decreases to that of unirradiated cell cultures if the cells are allowed to proliferate after irradiation, and we present evidence that this effect may be caused by an elimination of the cells carrying unrepaired DSBs. The results presented are in contrast to current models of risk assessment that assume that cellular responses are equally efficient at low and high doses, and provide the opportunity to employ gamma-H2AX foci formation as a direct biomarker for human exposure to low quantities of ionizing radiation.

0 comments Cited 330 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The impact of a negligent G2/M checkpoint on genomic instability and cancer induction.

Markus Lobrich, Penny A. Jeggo (2007)

DNA damage responses (DDR) encompass DNA repair and signal transduction pathways that effect cell cycle checkpoint arrest and/or apoptosis. How DDR pathways respond to low levels of DNA damage, including low doses of ionizing radiation, is crucial for assessing environmental cancer risk. It has been assumed that damage-induced cell cycle checkpoints respond to a single double strand break (DSB) but the G2/M checkpoint, which prevents entry into mitosis, has recently been shown to have a defined threshold of 10-20 DSBs. Here, we consider the impact of a negligent G2/M checkpoint on genomic stability and cancer risk.

0 comments Cited 192 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Radiologic and nuclear medicine studies in the United States and worldwide: frequency, radiation dose, and comparison with other radiation sources--1950-2007.

Mythreyi Bhargavan, B Thomadsen, Bret A Mettler … (2009)

The U.S. National Council on Radiation Protection and Measurements and United Nations Scientific Committee on Effects of Atomic Radiation each conducted respective assessments of all radiation sources in the United States and worldwide. The goal of this article is to summarize and combine the results of these two publicly available surveys and to compare the results with historical information. In the United States in 2006, about 377 million diagnostic and interventional radiologic examinations and 18 million nuclear medicine examinations were performed. The United States accounts for about 12% of radiologic procedures and about one-half of nuclear medicine procedures performed worldwide. In the United States, the frequency of diagnostic radiologic examinations has increased almost 10-fold (1950-2006). The U.S. per-capita annual effective dose from medical procedures has increased about sixfold (0.5 mSv [1980] to 3.0 mSv [2006]). Worldwide estimates for 2000-2007 indicate that 3.6 billion medical procedures with ionizing radiation (3.1 billion diagnostic radiologic, 0.5 billion dental, and 37 million nuclear medicine examinations) are performed annually. Worldwide, the average annual per-capita effective dose from medicine (about 0.6 mSv of the total 3.0 mSv received from all sources) has approximately doubled in the past 10-15 years. (c) RSNA, 2009.

0 comments Cited 174 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Biol Open

Journal ID (iso-abbrev): Biol Open

Journal ID (publisher-id): BIO

Journal ID (hwp): biolopen

Title: Biology Open

Publisher: The Company of Biologists Ltd

ISSN (Electronic): 2046-6390

Publication date Collection: 15 October 2018

Publication date (Electronic): 22 August 2018

Publication date PMC-release: 22 August 2018

Volume: 7

Issue: 10

Electronic Location Identifier: bio035113

Affiliations

[1 ]Department of Radiology, Maximiliansplatz 3, University of Erlangen , 91054 Erlangen, Germany

[2 ]Wisconsin Institutes of Medical Research, University of Wisconsin-Madison , Madison, Wisconsin 53705 USA

Author notes

[* ]Author for correspondence ( michael.brand@ 123456uk-erlangen.de )

Author information

Michael Brand http://orcid.org/0000-0003-2381-4536

Article

Publisher ID: BIO035113

DOI: 10.1242/bio.035113

PMC ID: 6215412

PubMed ID: 30135082

SO-VID: cf6907ac-04cf-4c7d-994d-8434a9f8f031

License:

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.

History

Date received : 22 April 2018

Date accepted : 16 August 2018

Funding

Funded by: National Institutes of Health, http://dx.doi.org/10.13039/100000002;

Award ID: R03 CA176799

Comments

Comment on this article

scite_

Cited by 4

See all cited by

Most referenced authors 307

See all reference authors

Reduction of X-ray-induced DNA damage in normal human cells treated with the PrC-210 radioprotector

Read this article at

ABSTRACT

Abstract

Related collections

When did Helicobacter first colonise humans?

Most cited references 33

Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses.

The impact of a negligent G2/M checkpoint on genomic instability and cancer induction.

Radiologic and nuclear medicine studies in the United States and worldwide: frequency, radiation dose, and comparison with other radiation sources--1950-2007.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 289

Cited by 4

Most referenced authors 307