Effects of Ionizing Radiation in Cancer Radiotherapy

Dear Colleagues,

For a long time, it was widely accepted that biological effects of ionizing radiation such as cell death, DNA damage and mutagenesis result from direct ionization of cell structures, particularly DNA, or from indirect damage through reactive oxygen species produced by radiolysis of water. This “targeted effect” (TE) model has been questioned by numerous observations, in which cells, that were not directly irradiated, exhibited responses similar to those of the directly irradiated cells. Therefore, it is nowadays accepted that the detrimental effects of ionizing radiation are not restricted only in the irradiated cells, but also to non- irradiated adjacent or distant cells.

Non-targeted effects (NTE) of ionizing radiation, which include genomic instability, radiation-induced bystander effects, and abscopal effects, are defined as the occurrence of biological effects in non-irradiated cells because of irradiation of other cells in the population. In opposition with TE, that display a linear dose-response, NTE exhibit a non-linear dose–response, with a marked effect at low doses of radiation. The related cellular and molecular mechanisms of NTE are still not completely understood, as they are mainly dependent on the cell type and the radiation quality. It is now widely admitted that in specific conditions, irradiated cells produce stress factors, which affect non-irradiated cells in the close environment (Bystander effect) or at distance (Abscopal effect). The cellular response, observed in non-irradiated cells, can be very similar to the response of irradiated cells, with a modulated intensity. NTE involve the secretion or the release by irradiated cells of a broad range of stress factors, from cytokines and specifically secreted molecules to reactive oxygen species or oxidized cellular wastes. In the case of communication between neighborhood cells, the stress factors can disseminate through gap junctions, or in case of distance communication, through small vesicles containing various embedded molecules. NTE are commonly studied as low-dose radiation effects in radioprotection, in association with genomic instability, mutation induction, and secondary cancer risk.

In a radiotherapy context, TE and NTE can be involved at the same time and in case of NTE, it could present several risks of complications when the irradiated area is very close to a sensitive organ. On the other hand, NTE could increase the biological effect of the radiotherapy on distant non-irradiated cancer cells (such as metastases) with immune associated effects (Abscopal effect) or on non-irradiated cancer cells adjacent to cancer cells specifically targeted with radioactive antibodies (positive Bystander effect).

I am pleased to invite you to participate to this Special Issue "Targeted and non-targeted effects of ionizing radiation in a context of cancer radiotherapy ". Research papers, up-to-date review articles, and commentaries are all welcome.

Dr. François Chevalier
Guest Editor

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