Ohnuma T, Arkin H, Minowada J, Holland J F
J Natl Cancer Inst. 1978 Apr;60(4):749-52. doi: 10.1093/jnci/60.4.749.
After previous work from this laboratory revealed that asparaginase was 800-2,000 times more inhibitory against human T-lymphocytes in culture than against B-lymphocytes, a similar further study of 13 chemotherapeutic and immunosuppressive agents was done. Cytosine arabinoside and 5-fluorouracil also had differential inhibitory activities on human T- and B-cells in culture. On the basis of the dose producing 50% inhibition of viable cell growth on day 5, cytosine arabinoside had 45-80 times more inhibitory activity against T-cells than against B-cells. In contrast to asparaginase and cytosine arabinoside, 5-fluorouracil had 10-20 times more inhibitory activity against B-cells. The rest of the chemotherapeutic and immunosupressive agents tested had minor or no differential activity. These findings indicated that T-cell response to asparaginase and cytosine arabinoside and B-cell response to 5-fluorouracil may be exploitable for the differential immunosuppressive effects presumed to be active in vivo. In addition, such differential responses may predict differential tumor cell behavior against these chemotherapeutic agents by T- and B-cell neoplasms in vivo.
此前该实验室的研究表明,在培养环境中,天冬酰胺酶对人T淋巴细胞的抑制作用比对B淋巴细胞强800 - 2000倍。之后,针对13种化疗和免疫抑制药物进行了类似的深入研究。阿糖胞苷和5-氟尿嘧啶在培养环境中对人T细胞和B细胞也具有不同的抑制活性。以第5天使活细胞生长抑制50%的剂量为依据,阿糖胞苷对T细胞的抑制活性比对B细胞高45 - 80倍。与天冬酰胺酶和阿糖胞苷不同,5-氟尿嘧啶对B细胞的抑制活性比对T细胞高10 - 20倍。其余所测试的化疗和免疫抑制药物具有较小的差异活性或无差异活性。这些发现表明,天冬酰胺酶和阿糖胞苷对T细胞的作用以及5-氟尿嘧啶对B细胞的作用,可能有助于实现体内假定存在的不同免疫抑制效果。此外,这种不同的反应可能预示着T细胞和B细胞肿瘤在体内对这些化疗药物的肿瘤细胞行为存在差异。