Interactions between tumor subpopulations affecting their sensitivity to the antineoplastic agents cyclophosphamide and methotrexate.
Interactions between tumor subpopulations affecting their sensitivity to the antineoplastic agents cyclophosphamide and methotrexate.
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发表时间：
1981-11
期刊：
影响因子：
11.2
通讯作者：
B. Miller;F. Miller;G. Heppner
中科院分区：
文献类型：
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作者：
B. Miller;F. Miller;G. Heppner
摘要：本文利用来自同一肿瘤的一组小鼠乳腺肿瘤亚群，研究了对化疗药物敏感性不同的肿瘤亚群之间相互影响的假设。在一组实验中，在同基因小鼠的两侧注射环磷酰胺（CY）敏感系168细胞和相对不敏感系410细胞。其他小鼠只接受双侧注射168或410个细胞。2 d后开始给药，每周1次，连用4周。168号线肿瘤的敏感性不受410号线肿瘤的影响，但410号线肿瘤的敏感性因168号线肿瘤的存在而增加。在肿瘤细胞注射前2天照射（400拉德）对细胞系168肿瘤增加细胞系410肿瘤cy敏感性的能力没有改变。仅携带168系肿瘤或同时携带168系和410系肿瘤的小鼠对单次高剂量CY的急性毒性作用比携带410系肿瘤的小鼠更敏感，这表明对CY激活的影响是药物敏感性相互作用的原因。在第二组实验中，对甲氨蝶呤（MTX）敏感性不同的亚群细胞在体外存在或不存在MTX的情况下共培养。在mtx敏感系410.4细胞存在的情况下，67和168细胞的敏感性有所提高。另一个相对不敏感的群体T68H克隆8的细胞敏感性不受影响。因此，某些乳腺肿瘤亚群对CY和MTX的敏感性可能受到其他亚群存在的影响，这些亚群在单独测试时对这些药物的敏感性不同。
Abstract The hypothesis that individual tumor subpopulations which differ in sensitivity to chemotherapeutic agents can influence each other9s drug sensitivity was investigated using a set of mouse mammary tumor subpopulations derived from the same tumor. In one set of experiments, syngeneic mice were given injections of cyclophosphamide (CY)-sensitive line 168 cells and relatively insensitive line 410 cells on opposite flanks. Other mice received bilateral injections of only 168 or only 410 cells. CY administration was begun 2 days later and continued once a week for 4 weeks. The sensitivity of line 168 tumors was not affected by line 410 tumors, but the sensitivity of line 410 tumors was increased by the presence of line 168 tumors. The ability of line 168 tumors to increase the CY-sensitivity of line 410 tumors was not altered by irradiating (400 rads) the hosts 2 days before tumor cell injection. Mice bearing line 168 tumors only or both line 168 and line 410 tumors were more sensitive to the acute toxic effects of single, high doses of CY than were the line 410 tumor-bearing mice, suggesting that effects on CY activation are responsible for the drug sensitivity interaction. In a second set of experiments, cells of subpopulations which differed in sensitivity to methotrexate (MTX) were cocultured in vitro in the presence or absence of MTX. In the presence of MTX-sensitive line 410.4 cells, the sensitivity of cells of lines 67 and 168 was increased. The sensitivity of cells of another relatively insensitive population, T68H clone 8, was not affected. Thus, the sensitivity of some mammary tumor subpopulations to both CY and MTX can be influenced by the presence of other subpopulations that differ, when tested alone, in sensitivity to these agents.