Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Abstract

ObjectiveThe objective of our study was to explore a possible molecular mechanism by which ultraviolet (UV) biophotons could elicit bystander responses in reporter cells and resolve the problem of seemingly mutually exclusive mechanisms of a physical UV signal & a soluble factor-mediated bystander signal.MethodsThe human colon carcinoma cell line, HCT116 p53 +/+, was directly irradiated with 0.5 Gy tritium beta particles to induce ultraviolet biophoton emission. Bystander cells were not directly irradiated but were exposed to the emitted UV biophotons. Medium was subsequently harvested from UV-exposed bystander cells. The exosomes extracted from this medium were incubated with reporter cell populations. These reporter cells were then assayed for clonogenic survival and mitochondrial membrane potential with and without prior treatment of the exosomes with RNase.ResultsClonogenic cell survival was significantly reduced in reporter cells incubated with exosomes extracted from cells exposed to secondarily-emitted UV. These exosomes also induced significant mitochondrial membrane depolarization in receiving reporter cells. Conversely, exosomes extracted from non-UV-exposed cells did not produce bystander effects in reporter cells. The treatment of exosomes with RNase prior to their incubation with reporter cells effectively abolished bystander effects in reporter cells and this suggests a role for RNA in mediating the bystander response elicited by UV biophotons and their produced exosomes.ConclusionThis study supports a role for exosomes released from UV biophoton-exposed bystander cells in eliciting bystander responses and also indicates a reconciliation between the UV-mediated bystander effect and the bystander effect which has been suggested in the literature to be mediated by soluble factors.

The Complexity of the Homeopathic Healing Response Part 1: The Role of the Body as a Complex Adaptive System in Simillimum-Initiated Recovery from Disease

“…17,35 Additional considerations include evidence that (1) endogenous non-linear amplification processes include stochastic resonance, hormesis, and/or TDS; (2) nanostructures, including but not limited to DNA 82,83 or miRNA, 84 can generate weak electromagnetic and/or nano-scale biological signals that stimulate changes in nearby bystander cell biological systems. 83,[85][86][87] Biological systems are capable of amplifying signals from weak electromagnetic fields. 88 The correct medicine and living system recipient require communication of an individually relevant "message" 25 or information pattern at their interface.…”

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“…Previous reports have demonstrated that exosomes from irradiated cells can trigger apoptosis in unirradiated cells, an effect known as the bystander effect [39,40], and that hypoxic exosomes can upregulate angiogenesis [41,42]. However, our study further shows that exosome uptake by hypoxic cancer cells can be modulated by exposing the cells producing the exosomes to hypoxia and/or ionizing radiation.…”

Relevance of Non-Targeted Effects for Radiotherapy and Diagnostic Radiology

“…The second breakthrough was when it was shown that irradiation of organic matter (shells, fruits or cells) led to biophoton emission in the UVA range and that there seemed to be a physical component to the initial bystander signal [63][64][65][66]. A series of papers [67][68][69] linked the photon emissions to the extent of the BE and implicated both p53 and exosomes in the mechanism. (see Figure 1).…”

“…(see Figure 1). The definitive experiments isolated exosomes and showed that exosomes from cells which received the UVA signal from irradiated cells without medium transfer, could by themselves produce a BE in never irradiated cells [69]. UVA alone was already known to produce BE from research in the 1990's [70,71].…”