Taghian A, Budach W, Zietman A, Freeman J, Gioioso D, Suit H D
Edwin L. Steele Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Cancer Res. 1993 Oct 15;53(20):5018-21.
We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993) that the take rate of human xenografts in the s.c. tissue of severe combined immunodeficient (SCID) mice is significantly higher than that of nude mice. Earlier, this laboratory reported that the transplantability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of human and murine tumors in comparison with s.c. tissue in SCID mice; (b) the relative i.c. transplantability in SCID mice in comparison to nude mice; and (c) the influence of whole-body irradiation on i.c. transplantability of SCID and nude mice. The assay based on the number of cells required to transplant tumors into 50% of recipients (TD50) was used to describe the transplantability assays. Five human and four murine tumor cell lines were used. Concurrent TD50 assays were performed i.c. in whole-body irradiated and nonirradiated SCID and nude mice. Serial 2-10-fold dilutions of cells were injected in a 10-microliters volume into the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50S were significantly lower than the s.c. TD50S by a factor of 1.7-1580. The average enhancement ratio (s.c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No significant difference was found between the i.c. TD50S in SCID and in nude mice, contrary to the significant difference in s.c. TD50S between both strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID mice. In conclusion, despite the significantly lower s.c. TD50S of human xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immunoreactivities between nude and SCID mice in s.c. transplantability; however, for i.c. transplantability, nude mice behaved equally as well as SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immunoreactivity, although the immunoreactivity is significantly lower than that of nude mice.
我们已经证明（A. 塔吉安等人，《癌症研究》，53: 5012 - 5017, 1993），严重联合免疫缺陷（SCID）小鼠皮下组织中人异种移植物的接种率显著高于裸鼠。此前，本实验室报告称，在裸鼠中，肿瘤异种移植物的颅内（i.c.）注射移植性显著高于皮下注射。本研究的目的是评估：（a）与SCID小鼠皮下组织相比，人和鼠肿瘤的相对颅内移植性；（b）与裸鼠相比，SCID小鼠的相对颅内移植性；以及（c）全身照射对SCID和裸鼠颅内移植性的影响。基于将肿瘤移植到50%受体所需的细胞数量（TD50）的测定方法用于描述移植性测定。使用了五种人类和四种鼠类肿瘤细胞系。在全身照射和未照射的SCID和裸鼠中同时进行颅内TD50测定。将细胞以2 - 10倍系列稀释，以10微升体积注射到皮肤下方3毫米处的右侧顶叶。结果表明，在所有研究的肿瘤中，颅内TD50显著低于皮下TD50，相差1.7 - 1580倍。裸鼠中的平均增强率（皮下TD50/颅内TD50）是SCID小鼠中的两倍。SCID小鼠和裸鼠的颅内TD50之间未发现显著差异，这与两种品系小鼠皮下TD50之间的显著差异相反（A. 塔吉安等人，《癌症研究》，53: 5012 - 5017, 1993）。全身照射对裸鼠的颅内TD50没有显著影响；然而，它确实影响了SCID小鼠中三分之二的异种移植物。总之，尽管SCID小鼠中人异种移植物的皮下TD50显著较低，但颅内TD50与NCr/Sed - nu/nu裸鼠的几乎相似。这表明在皮下移植性方面，裸鼠和SCID小鼠之间存在不同的免疫反应性；然而，对于颅内移植性，裸鼠的表现与SCID小鼠一样好。SCID小鼠中显著的增强率进一步证明，尽管该品系小鼠的免疫反应性显著低于裸鼠，但仍表现出残余的全身免疫反应性。
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