Homogenous and Microbeam X-Ray Radiation Induces Proteomic Changes in the Brains of Irradiated Rats and in the Brains of Nonirradiated Cage Mate Rats

Abstract

To evaluate microbeam radiation therapy (MRT), for brain tumor treatment, the bystander effect in nonirradiated companion animals was investigated. Adult rats were irradiated with 35 or 350 Gy at the European Synchrotron Research Facility using homogenous irradiation (HR) or MRT to the right brain hemisphere. The irradiated rats were housed with nonirradiated rats. After 48 hours, all rats were euthanized and the frontal lobe proteome was analyzed using 2-dimensional electrophoresis and mass spectrometry. Proteome changes were determined by analysis of variance (P < .05). Homogenous irradiation 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. Microbeam radiation therapy increased HSP-71, FBA, and prohibitin, and decreased aconitase, dihydropyrimidinase, TPI, tubulin DLD, and pyruvate kinase. Cage mates with HR irradiated rats showed increased HSP-71 and FBA and decreased pyruvate kinase, DLD, and aconitase. Cage mates with MRT irradiated rats showed increased HSP-71, prohibitin, and FBA and decreased aconitase and DLD. Homogenous irradiation proteome changes indicated tumorigenesis, while MRT proteome changes indicated an oxidative stress response. The bystander effect of proteome changes appeared antitumorigenic and inducing radioresistance. This investigation also supports the need for research into prohibitin interaction with HSP-70/71 chaperones and cancer therapy.

Spatially fractionated radiation therapy: a critical review on current status of clinical and preclinical studies and knowledge gaps

“…An increased expression of genes involved in DNA repair, cell cycle arrest, heat shock protein (HSP) and apoptosis were observed in the cells of the valley regions after exposure of cell cultures to GRID therapy (Asur et al 2012, Asur et al 2015. Bystander effects have also been evident in MRT, both in vivo and in vitro (Lobachevsky et al 2015, Smith et al 2018.…”

“…Some positive bystander effects have been hypothesized to explain normal tissue sparing (Dilmanian et al 2007). Some experimental indirect evidence was reported including increased levels of HSP 71 turnover found in the non-irradiated brain hemisphere of rats (Smith et al 2018), which is known to protect against neurological disorders.…”

Non-Targeted Effects of Synchrotron Radiation: Lessons from Experiments at the Australian and European Synchrotrons

“…In the study conducted by Mothersill'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.…”

Application of Proteomics in the Discovery of Radiosensitive Cancer Biomarkers

“…Mass spectrometry (MS) has become an important tool for large-scale protein identification in proteomics ( 14 ). Currently, research of proteomics mainly focused on basic medicine, health screening, disease prevention, prognosis prediction, patient stratification, and the identification of new targets ( 15 – 18 ).…”