Masunaga Shin-ichiro, Ando Koichi, Uzawa Akiko, Hirayama Ryoichi, Furusawa Yoshiya, Koike Sachiko, Ono Koji
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Osaka, Sennan-gun, Japan.
Acta Oncol. 2008;47(6):1087-93. doi: 10.1080/02841860701821999.
To clarify the radiosensitivity of intratumor total and quiescent (Q) cells in vivo to accelerated carbon ion beams compared with gamma-ray irradiation.
SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. Then they received 290 MeV/u carbon ions or gamma-rays. Immediately or 12 hours after the irradiation, the radiosensitivity of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P+Q) tumor cells was determined from the BrdU non-treated tumors based on the micronucleus frequency and clonogenic cell survival.
The apparent difference in radiosensitivity between total and Q cell populations under gamma-ray irradiation was markedly reduced with carbon ion beam, especially with a higher linear energy transfer (LET) value. Clearer repair in Q cells than total cells through delayed assay under gamma-ray irradiation was efficiently inhibited with carbon ion beams, especially with a higher LET.
In terms of tumor cell-killing effect as a whole, including intratumor Q cells, carbon ion beams, especially with higher LET values, were very useful for suppressing the dependency on the heterogeneity within solid tumors as well as depositing radiation dose precisely.
阐明与γ射线照射相比,体内肿瘤内总细胞和静止(Q)细胞对加速碳离子束的放射敏感性。
携带SCC VII肿瘤的小鼠连续给予5-溴-2'-脱氧尿苷(BrdU)以标记所有肿瘤内增殖(P)细胞。然后它们接受290 MeV/u碳离子或γ射线照射。照射后立即或12小时,使用针对BrdU的免疫荧光染色,根据微核频率评估Q细胞的放射敏感性。基于微核频率和克隆形成细胞存活率,从未经BrdU处理的肿瘤中确定总(=P+Q)肿瘤细胞的放射敏感性。
碳离子束显著降低了γ射线照射下总细胞群和Q细胞群之间明显的放射敏感性差异,尤其是在线性能量转移(LET)值较高时。γ射线照射下通过延迟检测发现Q细胞比总细胞有更明显的修复,而碳离子束能有效抑制这种修复,尤其是LET较高时。
就包括肿瘤内Q细胞在内的整体肿瘤细胞杀伤效果而言,碳离子束,尤其是LET值较高的碳离子束,对于抑制实体瘤内异质性的依赖性以及精确沉积辐射剂量非常有用。