Bubeník J, Kieler J, Jandlová T, Símova J
Institute of Molecular Genetics, Czechoslovak Academy of Sciences, Flemingovo.
Anticancer Res. 1992 Sep-Oct;12(5):1695-8.
Experiments were designed to assess age-related changes in the transplantability of human tumours xenografted in congenitally athymic (nu/nu) mice. It has been found that the number of progressively growing human tumour xenografts decreased significantly with increasing age of BALB/c nu/nu recipients. These findings, taken together with a previously recognized increase in the frequency of endogenous interleukin 2 (IL-2)-producing cells with age of nu/nu mice, prompted us to investigate whether administration of exogenous IL-2 to young adult nu/nu mice could change the transplantability of human tumours in the mice. Peritumoral administration of exogenous interleukin 2 to 8-week-old nu/nu mice inhibited the growth of the human tumour xenografts. In vitro activation of nu/nu splenocytes with exogenous Il-2 resulted in the generation of killer cells which have been found to be cytolytic when allowed to react with human tumour targets in 51Cr cytotoxicity assay. In addition, it has been found that the percentage of IL-2-activated Thy 1.2+ and ASGM1+ cells substantially increased with increasing age of nu/nu spleen cell donors. These findings are compatible with the hypothesis that the observed age-related decrease in takes of human tumour xenografts might be determined by the increasing level of IL-2 production and subsequent maturation of IL-2-dependent effector cells.
实验旨在评估先天性无胸腺（裸鼠，nu/nu）小鼠体内异种移植的人类肿瘤移植性与年龄相关的变化。已发现，随着BALB/c裸鼠受体年龄的增加，逐渐生长的人类肿瘤异种移植物数量显著减少。这些发现，连同之前认识到的裸鼠体内内源性白细胞介素2（IL-2）产生细胞频率随年龄增加而增加的情况，促使我们研究向年轻成年裸鼠施用外源性IL-2是否会改变小鼠体内人类肿瘤的移植性。向8周龄裸鼠瘤周施用外源性白细胞介素2可抑制人类肿瘤异种移植物的生长。用外源性IL-2体外激活裸鼠脾细胞可产生杀伤细胞，在51Cr细胞毒性试验中，当这些杀伤细胞与人类肿瘤靶标反应时，已发现具有细胞溶解作用。此外，还发现，随着裸鼠脾细胞供体年龄的增加，IL-2激活的Thy 1.2+和ASGM1+细胞的百分比大幅增加。这些发现与以下假设相符：观察到的人类肿瘤异种移植物植入率与年龄相关的下降可能由IL-2产生水平的增加以及随后IL-2依赖性效应细胞的成熟所决定。
