Masunaga S, Ono K, Sakurai Y, Suzuki M, Takagaki M, Kobayashi T, Kinashi Y, Akaboshi M
Radiation Oncology Research Laboratory, Kyoto University, Osaka.
Jpn J Cancer Res. 1998 Jan;89(1):81-8. doi: 10.1111/j.1349-7006.1998.tb00483.x.
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.
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，与传统放疗和化疗一样，控制具有克隆形成潜力的静止肿瘤细胞对于治疗增益至关重要。给荷瘤小鼠连续注射5-溴-2'-脱氧尿苷（BrdU）以标记所有增殖细胞。在给予硼酸钠-10B（BSH）、dl-对硼苯丙氨酸-10B（BPA）或水合钆双胺（欧乃影）后，用不同镉（Cd）比的中子照射肿瘤，然后分离并用细胞松弛素B（一种胞质分裂阻滞剂）孵育。使用针对BrdU的免疫荧光染色测定未标记BrdU的细胞（静止细胞）中的微核（MN）频率，而总细胞的MN频率则从未经BrdU预处理的肿瘤中获得。在无药物情况下，静止细胞的MN频率低于总细胞，但中子照射降低了两者之间的γ射线敏感性差异。与γ射线相比，中子在静止细胞中的相对生物效能（RBE）大于总细胞，低Cd比中子往往表现出较大的RBE值。使用中子俘获化合物时，每个细胞群体的MN频率都会增加，尤其是在使用高Cd比中子时。BPA比BSH更能提高总细胞的MN频率。然而，用BPA处理的静止细胞的敏感性低于用BSH处理的静止细胞。在高Cd比中子中明显观察到这种趋势。与无药物单独照射相比，欧乃影仅略微增加了两个细胞群体中的MN频率。从提高静止细胞敏感性的角度来看，应在给予BSH后用高Cd比中子照射肿瘤。
