Smith Richard, Wang Jiaxi, Seymour Colin, Fernandez-Palomo Cristian, Fazzari Jennifer, Schültke Elisabeth, Bräuer-Krisch Elke, Laissue Jean, Schroll Christian, Mothersill Carmel
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Mass Spectrometry Facility, Department of Chemistry, Queen's University, Kingston, Ontario, Canada.
Dose Response. 2018 Jan 22;16(1):1559325817750068. doi: 10.1177/1559325817750068. eCollection 2018 Jan-Mar.
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 ( < .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.
为评估微束放射治疗（MRT）用于脑肿瘤治疗的效果，对未受照射的伴养动物的旁观者效应进行了研究。成年大鼠在欧洲同步辐射研究设施中，使用均匀照射（HR）或MRT对右脑半球进行35或350 Gy的照射。将受照射的大鼠与未受照射的大鼠饲养在一起。48小时后，对所有大鼠实施安乐死，并使用二维电泳和质谱分析法对额叶蛋白质组进行分析。通过方差分析（<.05）确定蛋白质组的变化。均匀照射使血清白蛋白、热休克蛋白71（HSP - 71）、磷酸丙糖异构酶（TPI）、果糖二磷酸醛缩酶（FBA）和抑制素增加，使二氢硫辛酰胺脱氢酶（DLD）和丙酮酸激酶减少。微束放射治疗使HSP - 71、FBA和抑制素增加，使乌头酸酶、二氢嘧啶酶、TPI、微管蛋白DLD和丙酮酸激酶减少。与接受HR照射的大鼠同笼饲养的大鼠显示HSP - 71和FBA增加，丙酮酸激酶、DLD和乌头酸酶减少。与接受MRT照射的大鼠同笼饲养的大鼠显示HSP - 71、抑制素和FBA增加，乌头酸酶和DLD减少。均匀照射引起的蛋白质组变化表明有肿瘤发生，而MRT引起的蛋白质组变化表明有氧化应激反应。蛋白质组变化的旁观者效应似乎具有抗肿瘤和诱导放射抗性的作用。这项研究还支持了对抑制素与HSP - 70/71伴侣蛋白相互作用及癌症治疗进行研究的必要性。
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