PLoS ONE：质子辐射或增强肿瘤的发展

近日，来自伯克利国家实验室等处的科学家发现，来自质子的辐射可以增强肿瘤发生的过程，该项研究或许使得我们开发出更好的方法来保护宇航员免受太空辐射，为我们更好地理解辐射给人体带来的影响提供基础。

质子是带电荷的亚原子颗粒，也是主要的宇宙辐射的辐射来源，研究者Francis表示，我们的研究发现了，在辐射治疗期间低剂量的质子辐射所引发的肿瘤发生风险。而且质子辐射可以增强进行性肿瘤发生的过程，这个过程被称为上皮间质变迁（EMT），其和癌症发展直接相关。EMT同样和辐射诱导的纤维化有关。

值得注意的是，这项研究揭示了单独的质子可以诱发正常人类上皮细胞的EMT相关改变。尽管在太空中接受的辐射相比放疗低的多。低剂量的质子或许也可以激发EMT并且导致潜在的不利作用。相关研究成果刊登在了近日的国际杂志PLoS One上。

编译自：NASA Investigates Proton Radiation Effects On Cells

doi:10.1371/journal.pone.0041249
PMC:
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Protons Sensitize Epithelial Cells to Mesenchymal Transition

Minli Wang1, Megumi Hada1, Janapriya Saha1, Deepa M. Sridharan2, Janice M. Pluth2, Francis A. Cucinotta3*

Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.