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

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.

• Authors: Yoon Hee Cho, Yang Jee Kim, Sunyeong Lee, Kyung-In Joung, Hai Won Chung, Sunmi Kim, Su Young Kim
• Journal: Genes & genomics (Genes Genomics) Vol. 42 Issue 6 Pg. 673-680 (06 2020) ISSN: 2092-9293 [Electronic] Korea (South)
• PMID: 32314273 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Cytarabine
• 3-aminobenzamide

Topics

• Adult
• Benzamides (pharmacology)
• Cells, Cultured
• Cytarabine (pharmacology)
• DNA Repair (drug effects)
• Female
• Humans
• Micronuclei, Chromosome-Defective (drug effects, radiation effects)
• Radiation Tolerance
• X-Rays