HETEROTRANSPLANTATION OF HUMAN MALIGNANT-TUMORS IN NUDE THYMUSLESS MICE .2. MALIGNANT-TUMORS INDUCED BY INJECTION OF CELL-CULTURES DERIVED FROM HUMAN SOLID TUMORS
HETEROTRANSPLANTATION OF HUMAN MALIGNANT-TUMORS IN NUDE THYMUSLESS MICE .2. MALIGNANT-TUMORS INDUCED BY INJECTION OF CELL-CULTURES DERIVED FROM HUMAN SOLID TUMORS
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DOI：
10.1093/jnci/52.3.921
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发表时间：
1974-01-01
影响因子：
10.3
通讯作者：
WILLIAMS, LJ
中科院分区：
文献类型：
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作者：
GIOVANELLA, BC;STEHLIN, JS;WILLIAMS, LJ
以1×105~2×107个细胞的剂量，将11株来源于人类恶性肿瘤的细胞系(黑色素瘤6株，纤维肉瘤2株，骨肉瘤1株，恶性畸胎瘤1株，转移癌1株)注入无病原体的裸鼠体内。7个细胞系产生了37个恶性肿瘤，如果不早些杀死老鼠，这些肿瘤就会变得很大。通常情况下，腹膜腔被侵犯，内脏被破坏。11只动物在濒临死亡或死于肿瘤时被杀。3例肿瘤转移至淋巴结，1例转移至肺部。在26个裸鼠的37个人类肿瘤中，只有3个自发消退，其中1个后来发展为快速增长的转移。所有裸鼠肿瘤均进行了培养和核型分析。所有人都有人类的核型。来自正常胚胎组织的五个人系也被注射到裸鼠体内。即使注射了1×108个细胞，并对动物进行了4个多月的随访，也没有人产生肿瘤。为了进一步研究裸鼠对正常细胞和肿瘤细胞的分化能力，注射了小鼠细胞系。3个肿瘤系(L.E.，能够在同基因小鼠中诱发肿瘤)中有3个产生了恶性肿瘤。一种(MEF IT)只需接种1×103个细胞。MEF1(在同基因动物中不产生肿瘤，在培养中以与MEF IT相同的速度生长的细胞系)即使在裸鼠体内注射4×108个细胞，并随访6个月或更长时间，也不会产生肿瘤。
Eleven cell lines derived in our laboratory from human malignant tumors (6 melanomas, 2 fibrosarcomas, 1 osteosarcoma, 1 malignant teratoma, 1 metastatic carcinoma of uncertain origin) were injected subcutaneously or lntradermally into pathogen-free “nude” thymusless mice at doses from 1×105to 2×107cells. Seven cell lines gave origin to 37 malignant tumors which reached large sizes if the mice were not killed earlier. Frequently, the abdominal cavity was invaded and internal organs were destroyed. Eleven animals were killed when moribund or died of their tumor. Three tumors metastasized to lymph nodes and 1 to the lungs. Of 37 human tumors in 26 nudes, only 3 spontaneously regressed and 1 of these host mice later developed a rapidly growing metastasis. All tumors in the nudes were cultured and karyotyped. All had a human karyotype. Five human lines derived from normal embryonary tissues were also injected into nude mice. None produced tumors, even when 1×108cells were injected and the animals followed for more than 4 months. To further study the capability of the nude to differentiate between normal and neoplastic cells, murine cell lines were injected. Three of 3 neoplastic lines (l.e., capable of inducing tumors in syngenic mice) produced malignant neoplasms. One (MEF IT) required an inoculum of only 1×103cells. MEF1 (a line not producing tumors in syngenic animals and growing in culture at the same rate of MEF IT) did not give origin to tumos even when 4×108cells were injected into the nudes and the animals followed for 6 months or more.