A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

Abstract

The induction of "bystander effects" i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy (60)Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10 min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure.

Comparative Analysis of Biological Effects Induced on Different Cell Types by Magnetic Fields with Magnetic Flux Densities in the Range of 1–60 mT and Frequencies up to 50 Hz

“…This effect has been demonstrated for both high-and low-linear energy transfer radiations, but it is usually larger for densely ionizing radiation such as α particles [44]. Interestingly, 10 min exposure to static and time-varying MFs generated by a standard 1.5 T MRI device, as typically set to perform a routine head scan protocol, induce a bystander response in human adherent epithelial cells derived originally from a foreskin primary culture and immortalized by the HPV virus (HPV-G cells) [45]. As shown in Figure 2, human myeloid leukaemia U937 cells undergo blebbing of their plasma membrane when cultivated for up to 6 h in conditioned medium harvested from PBLs that previously had been left under exposure for 24 h to a SMF of 6 mT.…”

Bystander Effects Induced by Medium From Irradiated Cells: Similar Transcriptome Responses in Irradiated and Bystander K562 Cells

“…These are caused by as yet poorly defined factors released by irradiated cells and include chromosomal aberrations and instability, sister chromatid exchanges, mutagenesis, micronucleation, cell death, changes in transcription and enzyme activities, and sometimes increased proliferation, differentiation, and neoplastic transformation (1)(2)(3)(4)(5)(6). Some studies implicate direct intercellular connections (gap junctions) in these processes (7)(8)(9)(10), whereas others show participation of cytokines or other factors secreted into the culture medium (11)(12)(13) or of physical factors (14). A role of reactive oxygen species (ROS) and nitrogen species and calcium signaling appears to be established; irradiated cells produce ROS and nitrogen species, whereas antioxidants or voltage-dependent calcium channel blockers reduce bystander effects (11,(15)(16)(17).…”

Relevance of Non-Targeted Effects for Radiotherapy and Diagnostic Radiology

“…With the advent of chip technology and advanced proteomics techniques, screening for relevant proteins and miRNAs became possible [62]. 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.…”