Cifone M A, Fidler I J
Proc Natl Acad Sci U S A. 1981 Nov;78(11):6949-52. doi: 10.1073/pnas.78.11.6949.
The metastatic stability of clones, which were derived from the murine UV-2237 fibrosarcoma and which exhibit low or high metastatic potential, was examined after 60-72 days of continuous growth in vitro and in vivo. Subclones of the high metastatic clone exhibited a 140-fold variation in the production of experimental pulmonary metastases after intravenous injection into syngeneic C3H- mice. In contrast, subclones from the low metastatic clone varied only slightly (8-fold). Using cloned cells from three mouse tumors with differing metastatic potential, we determined the spontaneous mutation rates of cells with low or high metastatic capacities with respect to the selective genetic markers, 6-thiopurine resistance or ouabain resistance, or both. In all cases, cells with high metastatic potential had a 3- to 7-fold increase in the rate of mutation (per cell generation) at both genetic loci, as compared with their low metastatic but tumorigenic cell controls. These results support the hypothesis that the evolution of tumors from the benign to the malignant state could be the consequence of acquired genetic instability in the neoplastic cells.
从具有低转移潜能或高转移潜能的小鼠UV - 2237纤维肉瘤中获得的克隆，在体外和体内连续生长60 - 72天后，检测其转移稳定性。高转移克隆的亚克隆在静脉注射到同基因C3H -小鼠体内后，实验性肺转移的产生表现出140倍的差异。相比之下，低转移克隆的亚克隆差异仅轻微（8倍）。使用来自三种具有不同转移潜能的小鼠肿瘤的克隆细胞，我们确定了具有低转移能力或高转移能力的细胞相对于选择性遗传标记物6 -硫代嘌呤抗性或哇巴因抗性或两者的自发突变率。在所有情况下，与低转移但具有致瘤性的细胞对照相比，具有高转移潜能的细胞在两个基因位点的突变率（每细胞世代）都增加了3至7倍。这些结果支持了这样的假设，即肿瘤从良性状态向恶性状态的演变可能是肿瘤细胞获得性遗传不稳定性的结果。
