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首页> 美国卫生研究院文献>Cancer Science >Responses of Total and Quiescent Cell Populations in Solid Tumors to Boron and Gadolinium Neutron Capture Reaction Using Neutrons with Two Different Energy Spectra
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Responses of Total and Quiescent Cell Populations in Solid Tumors to Boron and Gadolinium Neutron Capture Reaction Using Neutrons with Two Different Energy Spectra

机译：使用两种不同能谱的中子对固体肿瘤中总细胞和静止细胞群体对硼和d中子俘获反应的响应

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In neutron capture therapy, whose effectiveness depends on the tumor distribution of neutron capture compound and the neutron energy distribution, controlling quiescent tumor cells with clonogenic potential is critical for therapeutic gain, as is the case in conventional radio‐ and chemotherapy. Tumor‐bearing mice were continuously given 5‐bromo‐2′‐deoxyuridine (BrdU) to label all proliferating cells. After administration of sodium borocaptate‐10B (BSH), dl‐p‐boronophenylalanine‐10B (BPA) or gadodiamide hydrate (Omniscan), the tumors were irradiated with neutrons of different cadmium (Cd) ratio, and then isolated and incubated with cytochalasin‐B (a cytokinesis blocker). The micronucleus (MN) frequency in cells without BrdU labeling (quiescent cells) was determined using immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU. Without drugs, quiescent cells showed lower MN frequencies than total cells, but neutron irradiation reduced gamma‐ray sensitivity difference between the two. Relative biological effectiveness (RBE) of neutrons compared with gamma‐rays was greater in quiescent cells than in total cells, and low Cd ratio neutrons tended to exhibit large RBE values. With neutron capture compounds, MN frequency for each cell population was increased, especially when high Cd ratio neutrons were used. BPA increased the MN frequency for total cells to a greater extent than BSH. However, the sensitivity of quiescent cells treated with BPA was lower than that in BSH‐treated quiescent cells. This tendency was clearly observed in high Cd ratio neutrons. Omniscan only slightly increased the MN frequency in both cell populations, compared with irradiation alone, without drugs. From the viewpoint of increasing the quiescent cell sensitivity, tumors should be irradiated with high Cd ratio neutrons after BSH administration.
机译：在中子俘获疗法中，其有效性取决于中子俘获化合物的肿瘤分布和中子能量分布，控制具有克隆形成潜能的静态肿瘤细胞对于获得治疗至关重要，这与常规放射疗法和化学疗法一样。连续给荷瘤小鼠5-溴-2'-脱氧尿苷（BrdU）标记所有增殖细胞。给予硼captate- 10 B（BSH），dl-p-boronophenylalanine- 10 B（BPA）或加多二酰胺水合物（Omniscan）给药后，用中子照射肿瘤分离不同比例的镉（Cd），然后分离并与细胞松弛素B（胞质分裂阻滞剂）一起孵育。使用BrdU的免疫荧光染色确定了未标记BrdU的细胞（静止细胞）中的微核（MN）频率，而总细胞的微核（MN）频率则得自未经BrdU预处理的肿瘤。没有药物，静态细胞的MN频率要低于总细胞，但中子辐照降低了两者之间的伽马射线敏感性差异。静态细胞中的中子相对生物有效性（RBE）与伽马射线相比要强于全细胞，而低Cd比的中子往往具有较大的RBE值。使用中子捕获化合物，每个细胞群的MN频率都会增加，特别是在使用高Cd比的中子时。与BSH相比，BPA增加了整个细胞的MN频率。但是，用BPA处理的静态细胞的敏感性低于BSH处理的静态细胞的敏感性。在高Cd比的中子中可以清楚地观察到这种趋势。与不使用药物的单独照射相比，Omniscan仅轻微增加了两个细胞群的MN频率。从增加静态细胞敏感性的观点出发，在给予BSH后，应以高Cd比的中子照射肿瘤。

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