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DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker
Rotem Daudee1,2,3, Rafi Gonen1,2,3, Uzi German3
1a The Shraga Segal Department of Immunology, Microbiology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Radiation Research
|April 11, 2018
Summary
DNA topoisomerase I (topo I) activity decreases after radiation exposure, serving as a potential biomarker for ionizing radiation dose. This reduction, observed across various human cells and radiation types, correlates with exposure levels.
Area of Science:
- Biochemistry
- Molecular Biology
- Radiation Biology
Background:
- Accurate radiation dose assessment is crucial, especially when physical dosimetry is unavailable.
- Biological markers are essential for correlating biological changes with radiation exposure.
- Human DNA topoisomerase I (topo I) is a key nuclear enzyme sensitive to DNA damage.
Purpose of the Study:
- To investigate the potential of topo I as a biomarker for radiation exposure and dose.
- To examine the effect of different radiation types on cellular topo I activity.
Main Methods:
- Exposure of human cells (lymphocytes, MG-63, HPF) to beta, X-ray, and gamma radiation.
- Measurement of cellular catalytic activity of topo I.
- Analysis of enzyme-protein levels and post-translational modifications (ADP-ribosylation).
Main Results:
- Irradiation significantly reduced topo I DNA relaxation activity in all tested human cell types.
- The reduction in topo I activity correlated with the radiation dose.
- Enzyme-protein levels remained unchanged, but post-translational modification (ADP-ribosylation) was observed, reducing activity.
Conclusions:
- Decreased cellular topo I catalytic activity after low-dose ionizing radiation exposure can serve as a novel biomarker.
- Topo I modification, specifically ADP-ribosylation, underlies the observed activity reduction.
- An ELISA-based method for large-scale analysis of radiation-induced topo I modification is being developed.
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