INCREASING METASTATIC POTENTIAL IS ASSOCIATED WITH INCREASING GENETIC INSTABILITY OF CLONES ISOLATED FROM MURINE NEOPLASMS
INCREASING METASTATIC POTENTIAL IS ASSOCIATED WITH INCREASING GENETIC INSTABILITY OF CLONES ISOLATED FROM MURINE NEOPLASMS
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DOI：
10.1073/pnas.78.11.6949
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
FIDLER, IJ
中科院分区：
文献类型：
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作者：
CIFONE, MA;FIDLER, IJ
体外和体内连续生长60-72天后，检测低转移和高转移潜能的小鼠UV-2237纤维肉瘤克隆的转移稳定性。在静脉注射后，高转移克隆的亚克隆在实验性肺转移的产生上表现出140倍的变化。注射同基因C3H-小鼠。低转移克隆的亚克隆只有很小的变化(8倍)。用3种不同转移潜能的小鼠肿瘤克隆细胞，分别测定了低转移和高转移细胞在选择性遗传标记、6-硫嘌呤耐药和哇巴因耐药方面的自发突变率。在所有病例中，与低转移但致瘤的对照细胞相比，具有高转移潜力的细胞在这两个遗传位点上的突变率(每代细胞)增加了3-7倍。肿瘤从良性到恶性的演变可能是肿瘤细胞后天遗传不稳定的结果。
The metastatic stabilities of clones derived from the murine UV-2237 fibrosarcoma, with low or high metastatic potential were 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 i.v. injection into syngeneic C3H- mice. Subclones from the low metastatic clone varied only slightly (8-fold). Using cloned cells from 3 mouse tumors with differing metastatic potential, the spontaneous mutation rates of cells with low or high metastatic capacities were determined 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 3-7-fold increase in the rate of mutation (per cell generation) at both genetic loci as compared with their low metastatic but tumorigenic cell controls. The evolution of tumors from the benign to the malignant state could be the consequence of acquired genetic instability in the neoplastic cells.