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Effects of the DNA repair inhibitors, cytosine arabinoside and 3-aminobenzamide, on the frequency of radiation-induced micronuclei, nuclear buds, and nucleoplasmic bridges

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Abstract

Background

Micronuclei (MN), nuclear bud (NBud), and nucleoplasmic bridge (NPB) are suggested as biomarkers for radiation exposure; however, they have not been extensively studied to understand the underlying mechanisms responsible for their formation.

Objectives

To (1) validate NBud and NPB within the cytokinesis-blocked micronucleus (CBMN) assay as biomarkers for radiation exposure and (2) determine the effects of the DNA repair inhibitors, cytosine arabinoside (Ara C) and 3-aminobenzamide (3-AB) on radiation-induced MN, NBud, and NPB formation.

Methods

Human blood samples were irradiated with 0–3 Gy X-rays and subsequently treated with Ara C and 3-AB. CBMN and chromosome aberration assays were carried out to measure MN, NBud, and NPB and dicentric chromosomes, respectively.

Results

The frequency of radiation-induced MN, NBud, and NPB increased in a dose-dependent manner. The frequency of MN, NBud, and NPB was highly and positively correlated with the dicentric chromosome, a standard biomarker for biodosimetry (r > 0.98, p < 0.0001). Furthermore, Ara C increased the frequency of MN, NBud, and NPB, whereas 3-AB increased the frequency of MN and NPB, but not NBud. Further, the potentiating effect of Ara C on the frequency of MN, NBud, and NPB was greater than that of 3-AB.

Conclusion

Our results validate NBuds and NPBs as independent valuable markers of radiation exposure. Additionally, we suggest that different mechanisms are likely involved in the formation of NBuds and NPBs following X-irradiation; however, additional studies are warranted to better understand the contribution of distinct DNA repair pathways to the formation of radiation-induced damages.

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Acknowledgements

We specially thank Drs. Sung Whan Ha (Seoul National University College of Medicine) and Melisa Schelvan (University of Montana) for their expertise in radiation exposure and critical reading of this manuscript, respectively.

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Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT, 59812, USA

    Yoon Hee Cho

  2. Da Vinci College of General Education, Chung-Ang University, Dongjak-Gu, Seoul, Korea

    Yang Jee Kim

  3. Graduate School of Public Health, Seoul National University, Gwanak-Gu, Seoul, Korea

    Sunyeong Lee, Kyung-in Joung, Hai Won Chung & Sunmi Kim

  4. Department of Preventive Medicine, School of Medicine, Jeju National University, Jeju-si, 63243, Jeju Special Self-Governing Province, Korea

    Su Young Kim

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Contributions

YHC, YJK, HWC and SYK: conceived and designed the experiments; YHC, YJK and SL: performed the experiments; SYK: analyzed the data; YHC, YJK, KJ, SK, and SYK: wrote and revised the paper.

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Correspondence to Yoon Hee Cho or Su Young Kim.

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YHC, YJK, SL, KJ, HWC, SK, and SYK declare that they have no conflict of interest.

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Cho, Y.H., Kim, Y.J., Lee, S. et al. Effects of the DNA repair inhibitors, cytosine arabinoside and 3-aminobenzamide, on the frequency of radiation-induced micronuclei, nuclear buds, and nucleoplasmic bridges. Genes Genom 42, 673–680 (2020). https://doi.org/10.1007/s13258-020-00934-8

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