Table 1 List of signals that have been proposed as NTE potential mediators.

Nitric Oxide

Due to NO lipophilic nature and stability, it constitutes a possible vehicle with which irradiated cells activate response processes in adjacent non-irradiated cells; increase in micronuclei formation after IR was abrogated when a NO specific scavenger was used.

Nuclear Factor kappa B

Upon inhibition of NF-κB, a decreased frequency of mutations was observed in the cells studied.

Reactive oxygen species

ROS scavengers reduced the frequency of DNA double strand breaks (DSB) in cells subjected to media collected from irradiated cells.

Purinergic

Upon release from the cells act as intercellular signaling molecules in what is known as purinergic signaling, shown to be important in the response to IR- Their work also shown that ATE released from irradiated cells activate receptors in non-irradiated cells which are involved in DNA damage and repair response.

Biophotons

Radiation in the ultra violet (UV) light spectrum. These biophotons are emited by biological material as a response to stress. In the context of radiation and NTE, they have been implicated as a possible mechanism by which cells alert others about radiation-induced changes.

Oxidized extracellular DNA

Oxidized DNA fragments stimulate an increase in ROS production which leads to an adaptive response via nuclear translocation of NF-E2 related factor-2 (NRF2) and consequent antioxidant enzymes activation in non-irradiated cells.

Cell free Chromatin

Cell free chromatin that is released from dying cells is able to initiate DNA damage and inflammation in the neighbor cells.

Extracellular vesicles carrying:

MicroRNAs

Key players in the gene regulation in response to cellular irradiation.

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Mitochondrial DNA

EVs from irradiated cells that lack mitochondrial DNA (mtDNA) are not able to increase the levels of DNA damage in bystander (non-irradiated) cells.

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