Wood P J, Hirst D G
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Br J Cancer. 1989 Jul;60(1):36-40. doi: 10.1038/bjc.1989.215.
The ability of the calcium antagonists, cinnarizine and flunarizine, to enhance the radiosensitisation produced by the administration of an erythrocyte transfusion to anaemic, RIF-1 or SCCVII/St tumour bearing mice was determined. Erythrocyte transfusion alone increased radiation cell killing 10-fold in the RIF-1 tumour when given 0-4 h before X-rays. In contrast, the SCCVII/St showed only a 4-fold increase in sensitivity, apparent when erythrocytes were given 2-6 h before irradiation. The administration of 50 mg kg-1 cinnarizine or flunarizine to anaemic mice followed by erythrocyte transfusion 0 h before X-rays produced the same level of cell survival for both tumours, a 20-fold increase in cell killing for cinnarizine, and a 30-40-fold effect for flunarizine, even though at this time interval, the erythrocyte transfusion alone did not sensitise the SCCVII/St tumour to X-rays. Further investigations indicated, however, that the erythrocyte transfusion was necessary to achieve the sensitisation with the calcium antagonists, since giving flunarizine to anaemic mice alone only achieved a 4-fold increase in radiation cell killing. In addition, flunarizine given with erythrocyte transfusion 4 h before X-rays, in SCCVII/St, the optimal time for radiosensitisation in this tumour, did not further increase the level of cell killing achieved by flunarizine plus erythrocyte transfusion 0 h before X-rays.
研究了钙拮抗剂桂利嗪和氟桂利嗪增强红细胞输注对贫血的、携带RIF-1或SCCVII/St肿瘤的小鼠放疗增敏作用的能力。单独红细胞输注在X射线照射前0 - 4小时给予时，可使RIF-1肿瘤的辐射细胞杀伤增加10倍。相比之下，SCCVII/St肿瘤仅在照射前2 - 6小时给予红细胞时，敏感性增加4倍。给贫血小鼠腹腔注射50 mg/kg桂利嗪或氟桂利嗪，然后在X射线照射前0小时输注红细胞，两种肿瘤均产生相同水平的细胞存活，桂利嗪使细胞杀伤增加20倍，氟桂利嗪使细胞杀伤增加30 - 40倍，尽管在此时间间隔单独红细胞输注并未使SCCVII/St肿瘤对X射线敏感。然而，进一步研究表明，红细胞输注是钙拮抗剂实现增敏作用所必需的，因为单独给贫血小鼠腹腔注射氟桂利嗪仅使辐射细胞杀伤增加4倍。此外，在SCCVII/St肿瘤中，在X射线照射前4小时（该肿瘤放疗增敏的最佳时间）给予氟桂利嗪并同时输注红细胞，并未进一步提高在X射线照射前0小时给予氟桂利嗪加红细胞输注所达到的细胞杀伤水平。
