Frondoza C G, Trivedi S M, Humphrey R L
Cancer Treat Rep. 1982 Jul;66(7):1535-44.
Murine LPC-1 plasmacytoma is sensitive to treatment with cyclophosphamide (CY), and animals bearing this tumor in advanced stages can be cured with doses as small as 60 mg/kg. With repeated transfer of LPC-1 cells followed by subcurative CY therapy, we have developed from this CY-sensitive parent line (CY-S) a stable CY-resistant subline (CY-R) that is unaffected by doses as large as 250 mg/kg. Stability of this induced CY resistance in the absence of CY treatment has been demonstrated for greater than 14 transfer generations. The CY-R subline has been compared to the CY-S parent line and shown to be similar with respect to morphology, growth kinetics, survival time, synthesis of IgG 2a kappa M component, and DNA content and distribution. The CY-S parent line responds in vivo to CY analogs (ifosfamide and trofosfamide), as judged by decreased tumor mass and increased survival; the CY-R subline is resistant to the CY analogs. The response to carmustine (BCNU) was tested, and resistance to CY did not predict for response to this alkylating agent since the effect on both CY-S and CY-R lines was equal. The significance of the development of this CY-resistant subline and the implications for future research into the mechanisms of such resistance are discussed.
小鼠LPC - 1浆细胞瘤对环磷酰胺（CY）治疗敏感，患有晚期这种肿瘤的动物用低至60mg/kg的剂量即可治愈。通过反复传代LPC - 1细胞并进行亚治愈剂量的CY治疗，我们从这个对CY敏感的亲代细胞系（CY - S）培育出了一个稳定的对CY耐药的亚系（CY - R），该亚系不受高达250mg/kg剂量的影响。在无CY治疗的情况下，这种诱导产生的CY耐药性在超过14代传代中保持稳定。已将CY - R亚系与CY - S亲代细胞系进行比较，结果表明在形态学、生长动力学、存活时间、IgG 2a κ M成分的合成以及DNA含量和分布方面二者相似。CY - S亲代细胞系在体内对CY类似物（异环磷酰胺和曲磷胺）有反应，表现为肿瘤体积减小和存活时间延长；CY - R亚系对CY类似物耐药。测试了对卡莫司汀（BCNU）的反应，对CY的耐药性并不能预测对这种烷化剂的反应，因为对CY - S和CY - R细胞系的影响是相同的。本文讨论了这种CY耐药亚系产生的意义以及对未来此类耐药机制研究的启示。
