Department of Cell Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Life Sci Space Res (Amst). 2018 Nov;19:31-42. doi: 10.1016/j.lssr.2018.08.002. Epub 2018 Aug 18.
There are considerable health risks related to ionizing and proton radiation exposure. While there is a long history of health risks associated with ionizing (photon) radiation exposure, there is a limited understanding of the long-term health risks associated with proton radiation exposure. Since proton radiation is becoming more common in cancer therapy, the long-term biological effects of proton radiation remain less well characterized in terms of radiotherapy and well as for astronauts during deep space explorations. In this study, we compared the long-term side effects of proton radiation to equivalent doses of X-rays in the initiation and progression of premalignant lesions in a lung cancer susceptible mouse model (K-ras). We show proton irradiation causes more complex DNA damage that is not completely repaired resulting in increased oxidative stress in the lungs both acutely and persistently. We further observed K-ras mice irradiated with protons had an increased number and size of initiated and premalignant lesions and adenomas that were often infiltrated with inflammatory cells. Proton irradiated mice had a lower median survival and increased carcinoma incidence as compared to unirradiated controls and X-rays exposed mice. Our conclusion is that exposure to proton irradiation enhances the progression of premalignant lesions to invasive carcinomas through persistent DNA damage, chronic oxidative stress, and immunosuppression.
电离辐射和质子辐射暴露会带来相当大的健康风险。虽然电离（光子）辐射暴露与健康风险的关联已有很长的历史，但对质子辐射暴露相关的长期健康风险的了解有限。由于质子辐射在癌症治疗中越来越普遍，质子辐射的长期生物学效应在放射治疗方面以及在深空探索期间的宇航员方面的特征仍不明显。在这项研究中，我们比较了质子辐射与 X 射线在肺癌易感小鼠模型（K-ras）中引发和进展前期病变的长期副作用。我们发现质子辐照会导致更复杂的 DNA 损伤，这些损伤无法完全修复，导致肺部的氧化应激在急性和持续性增加。我们还观察到，用质子辐照的 K-ras 小鼠的起始和前期病变以及腺瘤的数量和大小增加，并且经常有炎症细胞浸润。与未辐照对照和 X 射线暴露的小鼠相比，质子辐照的小鼠的中位生存期降低，癌发生率增加。我们的结论是，暴露于质子辐照会通过持续的 DNA 损伤、慢性氧化应激和免疫抑制，增强前期病变向浸润性癌的进展。
