Sharma S, Hill C K
University of Southern California School of Medicine, Department of Radiation Oncology, Albert Soiland Cancer Research Laboratory, Los Angeles 90015, USA.
Radiat Res. 1996 Mar;145(3):331-6.
To date, few studies have evaluated the magnitude of the risks of somatic effects in humans from low-dose or protracted radiation exposure to neutrons using in vitro or in vivo techniques (A. Kronenberg, Radiat. Res. 128, S87-S93, 1991). In earlier study a strong energy dependence was shown for neutron-induced mutations at both the hprt and the tk loci in a rodent fibroblast cell line (Zhu and Hill, Radiat. Res. 139, 300-306, 1994). Using fast neutrons produced by impinging protons on a beryllium target at the UCLA/VA cyclotron, we have been examining the energy dependence of mutation induction at the HPRT locus in a human epithelial cell line derived from solid tumor tissue. In the present study, human epithelial teratocarcinoma cells were exposed to neutron beams produced from protons with 46, 30, 20 and 14 MeV energy. We found that cytotoxicity increased by 50% as the neutron beams produced from 46 MeV to 14 MeV, confirming many earlier reports. But as with the Chinese hamster cells, the mutation frequency at the HPRT locus increased 2.5-4-fold with decreasing neutron energy. Additionally, although there was a strong energy dependence for mutation induction, we noted that the shape of the induction curves was curvilinear for the human cells compared to the linearity of the curves obtained for the Chinese hamster cells and some other non-solid tissue human cell lines. Calculations of the RBE, using gamma rays as the standard reflected these differences. The RBE for mutation at the HPRT locus was dependent not only upon energy but also on dose, giving rise to RBEs that were in some cases distinctly different from those found in the Chinese hamster cell line. In the low-dose region (doses below 75 cGy) the maximum RBE of about 5 resulted from irradiation by the lowest-energy neutron beam (14 MeV protons on beryllium).
迄今为止，很少有研究使用体外或体内技术评估低剂量或长期中子辐射照射对人类体细胞效应的风险程度（A. Kronenberg，《辐射研究》128，S87 - S93，1991）。在早期研究中，已表明啮齿动物成纤维细胞系中hprt和tk位点的中子诱导突变存在强烈的能量依赖性（Zhu和Hill，《辐射研究》139，300 - 306，1994）。利用在加州大学洛杉矶分校/退伍军人事务部回旋加速器中用质子撞击铍靶产生的快中子，我们一直在研究源自实体瘤组织的人上皮细胞系中HPRT位点突变诱导的能量依赖性。在本研究中，将人上皮性畸胎癌细胞暴露于由能量为46、30、20和14 MeV的质子产生的中子束。我们发现，从中子束能量为46 MeV降至14 MeV时，细胞毒性增加了50%，这证实了许多早期报告。但与中国仓鼠细胞一样，随着中子能量降低，HPRT位点的突变频率增加了2.5至4倍。此外，尽管突变诱导存在强烈的能量依赖性，但我们注意到，与中国仓鼠细胞和其他一些非实体组织人细胞系获得的曲线的线性相比，人细胞的诱导曲线形状是曲线形的。以γ射线为标准计算相对生物学效应（RBE）反映了这些差异。HPRT位点突变的RBE不仅取决于能量，还取决于剂量，导致在某些情况下RBE与中国仓鼠细胞系中的明显不同。在低剂量区域（剂量低于75 cGy），最低能量中子束（铍上14 MeV质子）照射产生的最大RBE约为5。
