Chaouni Samia, Leduc Alexandre, Pouzoulet Frédéric, De Marzi Ludovic, Megnin-Chanet Frédérique, Stefan Dinu, Habrand Jean-Louis, Sichel François, Laurent Carine
Cancer Centre François Baclesse, Normandy University, UNICAEN, UNIROUEN, ABTE-EA4651, 14076 Caen, France.
Translational Research Department, Experimental Radiotherapy Platform Institut Curie, PSL Research University, 91401 Orsay, France.
Antioxidants (Basel). 2020 Nov 24;9(12):1170. doi: 10.3390/antiox9121170.
Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.
质子治疗的副作用研究较少。此外，当质子束采用扫描而非散射方式时，未考虑剂量传递方式对正常组织的差异。我们在此提议在小鼠模型中研究质子束两种传递方式对血液、皮肤、肺和心脏的影响。为此，在布拉格峰之前的平台期，通过双散射（DS）或笔形束扫描（PBS）用190.6 MeV质子束对C57BL/6小鼠进行全身照射。评估小鼠存活率。照射三个月后取出血液和器官。测量遗传毒性、氧化应激和炎症的生物标志物。结果显示，即使在照射后3个月，质子照射仍会增加淋巴细胞微核频率、肺超氧化物歧化酶活性、红细胞和皮肤谷胱甘肽过氧化物酶活性、红细胞过氧化氢酶活性、肺、心脏和皮肤氧化型谷胱甘肽水平、红细胞和肺脂质过氧化以及红细胞蛋白质羰基化。比较两种质子束传递方式时，小鼠存活率无差异。然而，与DS相比，PBS显著增加了淋巴细胞微核频率、红细胞谷胱甘肽过氧化物酶活性和心脏氧化型谷胱甘肽水平。这些结果指出在质子治疗中考虑剂量传递方式的必要性，因为它可能影响晚期副作用。
