Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions

Abstract

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term “relative dose effect” (RDE). This ratio is advantageous, as it allows for simple comparison of dose–response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2–15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy.

Dose–response curves for analyzing of dicentric chromosomes and chromosome translocations following doses of 1000 mGy or less, based on irradiated peripheral blood samples from five healthy individuals

“…Therefore, it is necessary to obtain the background frequency for the Tr analysis based on the method of analysis. Furthermore, Shin et al reported a difference in radiosensitivity between healthy individuals [ 32 ], suggesting it might be necessary to adjust the dose estimation by factors other than age.…”

Radiomic Analysis of CT Predicts Tumor Response in Human Lung Cancer with Radiotherapy

“…Radiation therapy is a crucial and cost-effective lung cancer curative treatment [ 1 ], and its curative effect largely depends on the radiosensitivity of tumor cells of the different patients [ 2 ]. So, the valuation of radiosensitivity with respect to radiotherapy has significant potential to contribute to further therapeutic gain.…”

Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

“…Exosomes are membrane-bound extracellular vesicles (50–150 nm) which are released by cells into the extracellular environment [ 20 ]. These are known to have an important role in the intercellular communication, such as tissue repair and the immune system, influencing cell phenotype as well as the nervous system [ 21 ]. The released exosomes interact with target cells through expressed growth factors, bioactive lipids and membrane receptors, which could cause a direct stimulation for the target cells [ 22 ].…”