Sakata K, Suzuki N, Majima H, Okada S
Department of Radiation Oncology, Faculty of Medicine, University of Tokyo, Japan.
J Radiat Res. 1995 Mar;36(1):17-30. doi: 10.1269/jrr.36.17.
Relationship of cure and surviving clonogenic cell number after various doses of X-irradiation was examined in multicellular spheroids of LCT1 human lung adenocarcinoma cells, LCT2 human lung small cell carcinoma cells and FSA1233 mouse fibrosarcoma cells. Some of these spheroids were cured at such doses that considerable number of clonogenic cells still survived after irradiation. Radiocurability was analyzed by comparing total clonogenic cell number in spheroids, cellular radiosensitivity and critical cell number Nc, i.e., the minimum number of clonogenic cells required to produce regrowth. (Nc-1) cells were killed by post-radiation processes and the larger the critical cell number, the more radiocurable. The LCT2 spheroids had the largest critical cell number and were most radiocurable. To investigate underlying mechanisms, modifying effect of heavily irradiated (HIR) tumor cells on the clonogenicity, i.e., plating efficiency of unirradiated tumor cells was investigated. Plating efficiencies with HIR cells showed significant decrease in LCT2 cells, no change in LCT1 cells and increase in FSA1233 cells. The results indicated that in case of LCT2 spheroids some of viable cells surrounded by dying or dead cells might have been killed with unknown toxic effect additional to direct irradiation effect. Thus, critical cell number analysis may be useful to quantify and to compare modifying effect of cellular/environmental factors in curing process of spheroids or tumors.
在LCT1人肺腺癌细胞、LCT2人肺小细胞癌细胞和FSA1233小鼠纤维肉瘤细胞的多细胞球体中，研究了不同剂量X射线照射后治愈与存活克隆形成细胞数量的关系。这些球体中的一些在照射后仍有相当数量的克隆形成细胞存活的剂量下被治愈。通过比较球体中的总克隆形成细胞数量、细胞放射敏感性和临界细胞数量Nc（即产生再生长所需的克隆形成细胞的最小数量）来分析放射可治愈性。(Nc - 1)个细胞在放射后过程中被杀死，临界细胞数量越大，放射可治愈性越高。LCT2球体的临界细胞数量最大，放射可治愈性最强。为了研究潜在机制，研究了重度照射（HIR）肿瘤细胞对未照射肿瘤细胞克隆形成能力（即接种效率）的影响。与HIR细胞共同培养时，LCT2细胞的接种效率显著降低，LCT1细胞无变化，FSA1233细胞增加。结果表明，在LCT2球体的情况下，一些被死亡或濒死细胞包围的活细胞可能除了直接照射效应外，还因未知的毒性作用而被杀死。因此，临界细胞数量分析可能有助于量化和比较细胞/环境因素在球体或肿瘤治愈过程中的调节作用。
