ESTRO 2024 - Abstract Book

S5343

Radiobiology - Tumour biology

ESTRO 2024

775

Digital Poster

Sodium ascorbate interaction with non-homologous end-joining repair

Mehran Hariri 1 , Eleftherios Papalanis 1 , Diana Spiegelberg 1 , Evgenii Plotnikov 2 , Kristina Viktorsson 3 , Bo Stenerlöw 1

1 Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden. 2 Tomsk Polytechnic University, Research School of Chemical and Biomedical Technologies, Tomsk, Russian Federation. 3 Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden

Purpose/Objective:

Pharmacological ascorbate showed positive effects in tumor radiosensitization, combination therapy, and reducing the side effects of chemotherapy. The cytotoxic effect of ascorbate is mainly through DNA damage from H2O2 and ROS overload. However, the type of DNA damage, involvement of DNA double-strand break (DSB), NHEJ repair pathway, and type of cell death are not fully understood. This information is crucial for optimizing radiochemotherapy treatments which mainly rely on DSB induction to cancer cells. In this work, we aimed to reveal the sodium ascorbate effect on DSB generation, NHEJ activation, and type of cell death.

Material/Methods:

In this regard, human colorectal cancer with two types of NHEJ deficiency (DNA-PKcs, XRCC4) and two other cell lines with intact NHEJ were employed to investigate clonogenicity, survival, 3D spheroid growth, DSB quantification, NHEJ activation, apoptosis, and necrosis.

Results:

The results showed dose-dependent reduction of survival and growth, without NHEJ involvement. Increasing ascorbate concentration yielded an excessive load of DSB in all studied cell lines associated with strong pan-nuclear staining of γH2AX and necrosis without apoptosis activation. Interestingly, these cellular responses were independent of cells' NHEJ functionality.

Conclusion:

This information demonstrated that ascorbate DSB generation may not activate NHEJ.

Keywords: Sodium ascorbate, DSB, NHEJ

References: