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Radiation Oncology
Published in: Radiation Oncology 1/2019

Open Access 01-12-2019 | Research

Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines

Authors: Vesna Todorovic, Ajda Prevc, Martina Niksic Zakelj, Monika Savarin, Andreja Brozic, Blaz Groselj, Primoz Strojan, Maja Cemazar, Gregor Sersa

Published in: Radiation Oncology | Issue 1/2019

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Abstract

Background

Treatment options for recurrent head and neck tumours in the previously irradiated area are limited, including re-irradiation due to radioresistance of the recurrent tumour and previous dose received by surrounding normal tissues. As an in vitro model to study radioresistance mechanisms, isogenic cells with different radiosensitivity can be used. However, they are not readily available. Therefore, our objective was to establish and characterize radioresistant isogenic human pharyngeal squamous carcinoma cells and to evaluate early radiation response in isogenic parental, radioresistant and radiosensitive cells.

Methods

Radioresistant cells were derived from parental FaDu cells by repeated exposure to ionizing radiation. Radiosensitivity of the established isogenic radioresistant FaDu-RR cells was evaluated by clonogenic assay and compared to isogenic parental FaDu and radiosensitive 2A3 cells. Additional phenotypic characterization of these isogenic cells with different radiosensitivity included evaluation of chemosensitivity, cell proliferation, cell cycle, radiation-induced apoptosis, resolution of DNA double-strand breaks, and DNA damage and repair signalling gene expression before and after irradiation.

Results

In the newly established radioresistant cells in response to 5 Gy irradiation, we observed no alteration in cell cycle regulation, but delayed induction and enhanced resolution of DNA double-strand breaks, lower induction of apoptosis, and pronounced over-expression of DNA damage signalling genes in comparison to parental cells. On the other hand, radiosensitive 2A3 cells were arrested in G2/M-phase in response to 5 Gy irradiation, had a prominent accumulation of and slower resolution of DNA double-strand breaks, and no change in DNA damage signalling genes expression.

Conclusions

We concluded that the emergence of the radioresistance in the established radioresistant isogenic cells can be at least partially attributed to the enhanced DNA double-strand break repair, altered expression of DNA damage signalling and repair genes. On the other hand, in radiosensitive isogenic cells the reduced ability to repair a high number of induced DNA double-strand breaks and no transcriptional response in DNA damage signalling genes indicate on a lack of adaptive response to irradiation. Altogether, our results confirmed that these isogenic cells with different radiosensitivity are an appropriate model to study the mechanisms of radioresistance.
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Metadata
Title
Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines
Authors
Vesna Todorovic
Ajda Prevc
Martina Niksic Zakelj
Monika Savarin
Andreja Brozic
Blaz Groselj
Primoz Strojan
Maja Cemazar
Gregor Sersa
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2019
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-019-1418-6

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