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移植甲基胆蒽诱导肉瘤的小鼠骨髓同种异体移植抗性丧失。

Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas.

作者信息

Kumar V, Bennett M

出版信息

J Natl Cancer Inst. 1975 Aug;55(2):489-92.

PMID:240033
Abstract

To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step "stem cell rescue" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No "suppressor cells" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells.

摘要

为了确定在患有肿瘤的小鼠中,负责同种异体骨髓干细胞排斥反应的效应细胞是否受到抑制,给C57BL/6(B6)小鼠接种了3-甲基胆蒽(MCA)诱导的肉瘤细胞。当肿瘤直径达到2.0 - 2.5厘米时,对这些小鼠以及未接种的对照B6和(BALB/c×A)F1(CAF1)动物进行照射,并在两步“干细胞拯救”实验的第一步中给予BALB/c骨髓细胞。四天后,将原宿主的脾细胞重新接种到与BALB/c骨髓细胞相容的经照射的CAF1二级宿主中,并针对B6抗原进行免疫。脾细胞移植5天后125I - 5-碘-2'-脱氧尿苷的脾摄取率(百分比)被用作细胞增殖的指标,并反映原宿主中干细胞的生长情况。BALB/c干细胞在患有肿瘤的B6小鼠中的生长情况与在CAF1原宿主中的生长情况相同,但被B6对照排斥。在接种骨髓细胞6小时后,BALB/c干细胞的播种效率以及同基因B6干细胞在患有肿瘤的B6小鼠脾脏中的生长增加了两倍。为了排除播种增加导致同种异体干细胞存活率更高的可能性,向对照B6原宿主中注入的DBA/2骨髓细胞比向患有肿瘤的B6和对照DBA/2小鼠中注入的更多。对照B6小鼠能够抵抗甚至7.5×10(6)个DBA/2骨髓细胞的生长,而患有肿瘤的B6小鼠则允许2.5×10(6)个细胞生长。在患有肿瘤的小鼠脾脏中未检测到能够抑制骨髓细胞同种异体移植反应的“抑制细胞”。因此,移植的同基因MCA诱导的肉瘤消除了小鼠排斥同种异体骨髓干细胞的能力。

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