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10 April 2018 DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker
Rotem Daudee, Rafi Gonen, Uzi German, Itzhak Orion, Zeev B. Alfassi, Esther Priel
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Abstract

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

©2018 by Radiation Research Society.
Rotem Daudee, Rafi Gonen, Uzi German, Itzhak Orion, Zeev B. Alfassi, and Esther Priel "DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker," Radiation Research 189(6), 652-660, (10 April 2018). https://doi.org/10.1667/RR14859.1
Received: 14 June 2017; Accepted: 1 November 2017; Published: 10 April 2018
JOURNAL ARTICLE
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