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.

Keywords: antitumorigenesis; bystander effect; homogenous irradiation; microbeam irradiation; proteomics.

Figure 1.

Representative 2-dimensional gel of a rat brain indicating the protein which were found to respond to direct homogenous radiation (HR) and microbeam radiation therapy (MRT) or in the brains of cage mate rats housed with those rats which received direct irradiation and also glial fibrillary acidic protein (GFAP); spot excised to confirm identification (refer to Discussion). (1) Aconitase, (2) dihydrolipoyl dehydrogenase (DLD), (3) dihydropyrimidinase, (4) fructose bisphosphate aldolase (FBA), (5) glial fibrillary acidic protein (GFAP), (6) heat shock protein 71 (HSP-71), (7) prohibitin, (8) pyruvate kinase, (9) serum albumin (S-Alb), (10) triosephosphate isomerase (TPI), and (11) tubulin.