## 5 RIBE and RIAE Studies at the AS and ESRF Synchrotron Facilities
### Studies at the ESRF
#### 5.2.2 Inter-Animal Communication of RIBE at the ESRF  
The Mothersill laboratory examined a concept first proposed by [PERSON] [117], who hypothesized that irradiated animals have the ability to communicate stressors via volatile compounds (Figure 4c). [PERSON]'s original study showed, first, that the urine of irradiated mice and rats was the source of the bystander signals and, second, that no physical contact between the urine and naive mice and rats was required for transmission of the bystander signals. They confirmed the latter by removing the bedding of the irradiated animals and placing it under the cage of the non-irradiated mice and rats. The bystander animals exhibited lower immunoreactivity than the control animals. Thus, since there was no physical contact, the bystander signals, which are yet to be identified, must have been transmitted via volatiles.  
There are no publications about specific chemical signals of pathological states and their effects on intact animals. The only exception are reports about \"fear smell\" release by stressed animals; this smell modifies the immunity of intact animals [117; 118]. [PERSON] et al. [117] speculate that under physiological conditions, syngeneic secretions can be attractive, while allogeneic secretions are immunosuppressive to intact animals. Presumably, this is a manifestation of emission of different chemical signals, with a biological purpose associated with the natural selection. At least in plants, methyl salicylate (MeSA) and methyl jasmonate (MeJA) serve as volatile signals communicating genome instability (as measured by an increase in the homologous recombination frequency) between UVC-irradiated plants and their unexposed neighbors [119].  
In the study conducted by [PERSON]'s team at the ESRF, Wistar rats exposed to localized BB or MRT were placed in the same cage with unirradiated animals [120]. After 48 h, the BB and MRT-exposed rats, as well as the unirradiated \"cage-mates\" were euthanized and tissues were collected to produce explant-conditioned media for the clonogenic reporter assay. Their results confirmed the transfer of bystander factors from the irradiated rats to completely unirradiated rats. This work was complemented by a subsequent study in which the bystander proteome was examined. BB radiation increased serum albumin, heat shock protein 71 (HSP-71), triosephosphate isomerase (TPI), fructose bisphosphate aldolase (FBA), and prohibitin and decreased dihydrolipoyl dehydrogenase (DLD) and pyruvate kinase in exposed animals. MRT-exposed animals demonstrated increased HSP-71, FBA,and prohibitin, and decreased aconitase, dihydropyrimidinase, TPI, tubulin DLD, and pyruvate kinase. The cage mates with BB irradiated rats showed increased HSP-71 and FBA and decreased pyruvate kinase, DLD, and aconitase, indicative of tumorigenesis. The cage mates of MRT-irradiated rats showed an increase in HSP-71, prohibitin, and FBA, and decreased aconitase and DLD, which, the authors believe, is indicative of an oxidative stress response and an antitumor bystander proteome that could also confer radioresistant properties.