Laurent Carine, Leduc Alexandre, Pottier Ivannah, Prévost Virginie, Sichel François, Lefaix Jean-Louis
SAPHYN (Santé Physique Nucléaire), ARCHADE (Advanced Resource Centre for Hadrontherapy in Europe) Program, Caen, France.
ABTE (Aliments, Bioprocédés, Toxicologie, Environnements), EA4651, Université de Caen-Basse Normandie, Caen, France ; CLCC (Centre de Lutte Contre le Cancer) François Baclesse, Caen, France.
PLoS One. 2013 Dec 23;8(12):e85158. doi: 10.1371/journal.pone.0085158. eCollection 2013.
Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D₀ (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D(10%) (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D(0%) (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this discrepancy between the two types of radiation should be investigated.
最近有报道称，碳离子（C离子）放射治疗后出现了皮肤并发症。氧化应激被认为是晚期皮肤反应出现的重要途径。我们评估了碳离子与X射线照射后正常人皮肤成纤维细胞中的氧化应激情况。计算了存活曲线和放射生物学参数。对DNA损伤、脂质过氧化（LPO）、蛋白质羰基化和抗氧化酶活性进行了定量分析。测定了还原型谷胱甘肽与氧化型谷胱甘肽的比率（GSH/GSSG）。评估了培养上清液中促炎细胞因子的分泌情况。在D₀（对应存活分数为37%的照射剂量）时，C离子相对于X射线的相对生物效能（RBE）为4.8。对于X射线和C离子，2 Gy时的存活分数（SF2）分别为71.8%和7.6%。与X射线相比，C离子照射后即时DNA损伤增加较少，但在D(10%)（对应存活分数为10%的照射剂量）时观察到后期增加。LPO产物和蛋白质羰基仅在C离子照射后24小时增加。X射线照射后，超氧化物歧化酶（SOD）活性在即时和第14天在D(0%)（对应存活分数约为0%的照射剂量）时强烈增加，过氧化氢酶活性未改变，谷胱甘肽过氧化物酶（GPx）活性仅在第14天增加。与X射线相比，C离子照射后这些活性降低。X射线照射后GSH/GSSG未改变，但C离子照射后立即降低，然后从第7天开始增加。X射线照射后期IL-6分泌增加。C离子照射后，IL-6浓度在第7天增加，但在后期低于X射线。与X射线相比,C离子对正常人皮肤成纤维细胞的影响似乎是有害的,因为它们会产生晚期DNA损伤、LPO产物和蛋白质羰基,并降低抗氧化防御能力。应研究导致这两种辐射之间存在差异的机制。
