Table 5.
Chronological summary of the pre-clinical studies about bystander and abscopal effects: the clonogenic the survival of brain cells after pencil beam and/or microbeam in-vivo irradiation (usually using a synchrotron) is compared with that of the corresponding not-targeted bladder cells.
| Reference | Animal model (strain) | Set-up | Endpoint (method) | Euthanasia timing after RT | Findings |
|---|---|---|---|---|---|
| Singh et al. (77) |
Female mouse (C57BL6 and Balb/c) |
Whole body irradiation (Co60 source) at single and serial low dose (20mGy-2Gy) | RIBE (clonogenic survival) |
24 h | Genotype determined the type of bystander signal/response |
| Fernandez-Palomo et al. (78) |
Rat (sex n.a.) (Wistar) |
17.5, 35, 70, 350 Gy delivered by synchrotron on one brain hemisphere | RIBE (clonogenic survival) |
4, 8, 12 h | Both MRT and HSR yielded a demonstrable abscopal effect after high doses of irradiation |
| Mothersill et al. (79) |
Male rat (Wistar) |
Whole body MRT and HSR on one brain hemisphere (35 and 350 Gy skin-entry doses) | RIBE (proteomics, clonogenic survival) |
48 h (hours in cage with uneradicated rats) |
Evidence of strong RIBE signal in the contra-lateral brain hemisphere and weaker effects in the distant bladder of the irradiated rats. Proximity to an irradiated animal induced signaling changes in an un-irradiated partner |
| Fernandez-Palomo et al. (80) |
Male rat (Fisher) |
MRT (20 or 200 Gy skin-entry doses) on one brain hemisphere with inoculated F98 cells | RIBE/abscopal effects (calcium flux, role of 5HT, clonogenic survival and proteomic profil) |
48 h (hours in cage with unirradiated rats) |
Membrane related functions were critical for true RIBE expression. Bystander effects (in partner animals) were not the same as abscopal effects (in the irradiated animal) |
| Fernandez-Palomo et al. (81) |
Male/female mouse (NU-Foxn1nu) |
PB (200 or 1,000 Gy skin-entry doses) and MRT (22 Gy or 110 Gy) on one brain hemisphere with and without glioma injected 7d earlier | RIBE/abscopal effects (calcium flux, clonogenic survival) |
2, 12, 48 h | Calcium data did not support a calcium channel mediated mechanism. The presence of a tumor reduced or reversed the effect. The immune response played a role. |
Thus, in this field of research the normal bladder does not deal with any direct radiation effect.
RT, radiotherapy; RIBE, radiation-induced bystander effects; PB, Pencil Beam; MRT, microbeam irradiation; HSR, homogenous synchrotron radiation.