Ionizing Radiation-Induced DNA Damage Response in Primary Melanocytes and Keratinocytes of Human Skin

Cytogenetic and Genome Research

Meador J.A.a· Morris R.J.b· Balajee A.S.c

Author affiliations

aCenter for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, New York, NY, USA
bHormel Institute, University of Minnesota, Austin, MN, USA
cCytogenetic Biodosimetry Laboratory, Radiation Emergency Assistance Center/Training Site, Oak Ridge Institute for Science and Education, Oak Ridge Associated Universities, Oak Ridge, TN, USA

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Article / Publication Details

First-Page Preview

Abstract of Original Article

Received: July 28, 2022
Accepted: September 09, 2022
Published online: December 05, 2022
Issue release date:

Number of Print Pages: 13
Number of Figures: 5
Number of Tables: 1

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

Abstract

Currently, our knowledge of how different cell types in a tissue microenvironment respond to low and high linear energy transfer (LET) radiation is highly restricted. In this study, a comparative analysis was performed on γ-ray-induced DNA damage and repair in primary human melanocytes and keratinocytes isolated from 3 donors. Our study demonstrates a modest interindividual variability in both melanocytes and keratinocytes in terms of both spontaneous and ionizing radiation (IR)-induced 53BP1 foci formation and persistence. Melanocytes, in general, showed a slightly elevated (1.66–2.79 folds more) 53BP1 foci induction relative to keratinocytes after exposure to different doses of γ-rays (0.1–2.5 Gy) radiation. To verify the influence of ATM kinase on IR-induced 53BP1 foci formation, melanocytes and keratinocytes were treated with a specific ATM kinase inhibitor (KU55993, 10 μM) for 1 h prior to radiation. ATM kinase inhibition resulted in the reduction of both spontaneous and IR-induced 53BP1 foci by 17–42% in both melanocytes and keratinocytes of all the 3 donors. Increased persistence of IR-induced 53BP1 foci number was observed in ATM-inhibited melanocytes and keratinocytes after different post exposure times (6 h and 24 h). Taken together, our study suggests that interindividual variations exist in the induction and repair of DNA double-strand breaks (DSBs) in melanocytes and keratinocytes and that ATM is crucial for an optimal DSB repair efficiency in both human skin cell types.

© 2022 S. Karger AG, Basel

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First-Page Preview

Abstract of Original Article

Received: July 28, 2022
Accepted: September 09, 2022
Published online: December 05, 2022
Issue release date:

Number of Print Pages: 13
Number of Figures: 5
Number of Tables: 1

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

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