Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada.
Int J Radiat Biol. 2013 Feb;89(2):118-27. doi: 10.3109/09553002.2013.732252. Epub 2012 Oct 23.
To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue.
Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry.
HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes.
These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention.
通过研究非照射组织中旁观者效应的诱导,进一步评估微束照射(MBI)作为一种潜在的无创脑肿瘤治疗方法的用途。
在欧洲同步辐射研究设施(ESRF),使用均匀(宽束)照射(HI)或仅照射右脑半球的高能微束,对成年大鼠进行 35 或 350Gy 的照射。然后使用二维电泳(2-DE)和质谱法分析额叶的蛋白质组。
HI 导致了肿瘤发生的蛋白质组反应;白蛋白、乌头酸酶和三磷酸异柠檬酸酶(TPI)增加,二氢乳清酸脱氢酶(DLD)减少。MBI 旁观者效应的蛋白质组变化表明活性氧介导的细胞凋亡;TPI、抑制素和微管蛋白减少,神经胶质纤维酸性蛋白(GFAP)增加。这些潜在的抗肿瘤凋亡蛋白质组变化也与神经退行性变有关。然而,旁观者效应也增加了热休克蛋白(HSP)71 的周转率。HSP71 已知可预防旁观者效应蛋白质组变化所特征化的所有神经紊乱。
这些结果表明,这些 MBI 诱导的旁观者效应蛋白的集体相互作用及其 HSP71 的介导,可能赋予一种保护作用,现在值得进一步的实验关注。