Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

Abstract

The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy).

X‐rays effects on cytoskeleton mechanics of healthy and tumor cells

“…Interestingly, the reduced proliferation of SVT2 cells is not because of a lowering of the percentage of cells able to enter S‐phase after X‐ray treatment (Supporting Information Fig. S1), suggesting that it is more likely that the X‐ray treatment is affecting either the S‐phase exit or G/2M transition (Nüsse, ; Iliakis et al, ; Suetens et al, ).…”

“…Nowadays, one of the most effective treatments for cancer is radiation therapy. The ability of ionizing radiation (IR) to induce dramatic consequences for the cell, by promoting the formation of radicals and reactive oxygen species (ROS) which damage DNA and lead to cell death, has been thoroughly investigated (Puck and Marcus, ; Puck, ; Nüsse, ; Iliakis et al, ; Suetens et al, ). But IR can also target other biologically essential macromolecules, such as lipids and proteins.…”

Stress and Radiation Responsiveness

“…Recently, ground-based studies on animals showed that exposure to particle radiation has a higher carcinogenic effect compared to photon exposure (Weil et al 2014;Suman et al 2015;Trani et al 2010). In addition, our lab performed many in vitro experiments with cancer cells exposed to carbon ions (Suetens et al 2016(Suetens et al , 2014(Suetens et al , 2015. Further studies in this field will definitely contribute in reducing the present uncertainties associated with cancer risk estimates on astronauts.…”

Molecular Signaling in Response to Charged Particle Exposures and its Importance in Particle Therapy

“…Ionizing radiation induces multiple genotoxic, stress-induced signaling pathways that regulate cellular growth, proliferation, cell cycle progression, DNA replication, DNA repair, cell death, apoptosis, and cell-cell adhesion [17][18][19]. That very efficient DDR signaling network ensures the integrity of the genome by cell-cycle checkpoints and DNA repair.…”