Masunaga S, Ono K, Sakurai Y, Takagaki M, Kobayashi T, Suzuki M, Kinashi Y, Akaboshi M
Radiation Oncology Research Laboratory, Kyoto University, Osaka, Japan.
Int J Radiat Oncol Biol Phys. 1998 Jul 15;41(5):1163-70. doi: 10.1016/s0360-3016(98)00149-7.
Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.
C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).
Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.
From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.
研究实体瘤中静止（Q）肿瘤细胞和总肿瘤细胞对三种不同镉（Cd）比例的中子照射的反应。还讨论了Q细胞在肿瘤控制中的作用。
携带SCC VII肿瘤的C3H/He小鼠使用植入式微型渗透泵连续5天给予5-溴-2'-脱氧尿苷（BrdU），以标记所有增殖（P）细胞。腹腔注射硼卡钠-10B（BSH）30分钟后，或口服dl-对硼苯丙氨酸-10B（BPA）3小时后，用中子照射肿瘤，或对未使用10B化合物的肿瘤进行γ射线照射。使用三种不同镉（Cd）比例的中子进行这种中子照射。然后切除肿瘤，切碎并胰蛋白酶消化。将肿瘤细胞悬液与细胞松弛素-B（一种胞质分裂阻滞剂）一起孵育，并使用针对BrdU的免疫荧光染色确定未标记BrdU的细胞（Q细胞）中的微核（MN）频率。从未用BrdU预处理的肿瘤中确定总（P + Q）肿瘤细胞中的MN频率。根据双核肿瘤细胞中诱导微核的频率（MN频率）评估对中子的敏感性。
在没有10B化合物的情况下，Q细胞中的MN频率低于总细胞群体中的MN频率。中子照射降低了总细胞和Q细胞之间的敏感性差异。与γ射线相比，中子在Q细胞中的相对生物效应（RBE）大于总细胞中的RBE，低Cd比例中子的RBE值往往高于高Cd比例中子的RBE值。使用10B化合物时，每个细胞群体的MN频率都会增加，尤其是总细胞。当使用高Cd比例中子时，MN频率的这种增加更为明显。BPA比BSH更能增加总肿瘤细胞的MN频率。然而，用BPA处理的Q细胞的敏感性低于用BSH处理的Q细胞。在高Cd比例中子中清楚地观察到这种趋势。
从提高Q细胞敏感性的角度来看，应在给予BSH后用高Cd比例中子照射肿瘤。然而，由于其低肿瘤与正常组织以及肿瘤与血液的生物分布比率，正常组织反应仍有待研究。
