Chow D A, Ray M, Greenberg A H
Int J Cancer. 1983 Jan 15;31(1):99-105. doi: 10.1002/ijc.2910310116.
The stability of a cloned murine tumor for sensitivity to NR was examined following growth in vivo in order to test the hypothesis that tumor progression proceeds through the generation and selection of variants. Clonal sensitivity to the [131I]-dUrd elimination assay of NR was assessed for the L5178Y-F9 tumor grown in syngeneic DBA/2 mice or maintained solely in tissue culture. Subclones derived from a tumor obtained from the injection site 3 1/2 weeks after the s.c. inoculation of 25 cells were less sensitive to NR in comparison with subclones derived from cells grown only in vitro. Subclones from the cells grown in vivo exhibited increased heterogeneity in sensitivity to NR in addition to their expanded range of susceptibility to complement-mediated lysis by CBA serum natural antibodies. The extent of the heterogeneity argues against tumor "adaptation" forming the basis for the phenotypic alteration while chromosomal studies eliminate the possibility that a new tumor was induced. These data support the hypothesis that tumor progression proceeds through the random generation of variants and host-mediated selection for the proliferation of clones with an increased ability to survive.
为了验证肿瘤进展是通过变异体的产生和选择这一假说，在体内生长后检测了克隆的鼠肿瘤对NR敏感性的稳定性。对同基因DBA/2小鼠体内生长的或仅在组织培养中维持的L5178Y - F9肿瘤，评估其对NR的[131I]-dUrd消除试验的克隆敏感性。与仅在体外生长的细胞衍生的亚克隆相比，从皮下接种25个细胞3.5周后从注射部位获得的肿瘤衍生的亚克隆对NR的敏感性较低。体内生长的细胞衍生的亚克隆除了对CBA血清天然抗体介导的补体溶解的敏感性范围扩大外，对NR的敏感性还表现出增加的异质性。异质性的程度反对肿瘤“适应”构成表型改变的基础，而染色体研究排除了诱导新肿瘤的可能性。这些数据支持肿瘤进展是通过变异体的随机产生和宿主介导的对生存能力增强的克隆增殖的选择这一假说。
