Reeve J G, Wright K A, Workman P
Br J Cancer. 1984 Aug;50(2):153-8. doi: 10.1038/bjc.1984.157.
The response of clonal subpopulations isolated from the RIF-1 mouse sarcoma to melphalan treatment is independent of cell ploidy, whereas a clear relationship exists between ploidy and cell sensitivity to CCNU treatment. In the present study RIF-1 clones have been exposed to nitrogen mustard, aniline mustard and chlorambucil, and to nitrosoureas BCNU, MeCCNU and chlorozotocin, in order to evaluate whether or not the different physiochemical and biological activities of these agents would affect the patterns of drug sensitivity obtained for melphalan and CCNU. Irrespective of the different lipophilicities, transport properties and chemical reactivities of the nitrogen mustards, RIF-1 clones showed the same pattern of sensitivity as previously observed for melphalan. Similarly, RIF-1 clones when exposed to nitrosoureas BCNU, MeCCNU and chlorozotocin, showed the same pattern of sensitivity as that obtained for CCNU exposure. These data suggest (a) that the variation in the sensitivity of RIF-1 clones to treatment by the nitrogen mustards is unlikely to reflect differences in either membrane permeability or in drug transport and (b) that the ploidy dependent nitrosourea responses shown by RIF-1 clones similarly do not reflect differences in drug uptake.
从RIF-1小鼠肉瘤中分离出的克隆亚群对美法仑治疗的反应与细胞倍性无关，而倍性与细胞对洛莫司汀治疗的敏感性之间存在明显关系。在本研究中，RIF-1克隆已暴露于氮芥、苯胺芥子气和苯丁酸氮芥，以及亚硝基脲类药物卡莫司汀、司莫司汀和氯脲霉素，以评估这些药物不同的物理化学和生物学活性是否会影响美法仑和洛莫司汀的药物敏感性模式。无论氮芥的亲脂性、转运特性和化学反应性如何不同，RIF-1克隆对氮芥的敏感性模式均与先前观察到的美法仑相同。同样，RIF-1克隆在暴露于亚硝基脲类药物卡莫司汀、司莫司汀和氯脲霉素时，其敏感性模式与暴露于洛莫司汀时相同。这些数据表明：（a）RIF-1克隆对氮芥治疗敏感性的差异不太可能反映膜通透性或药物转运的差异；（b）RIF-1克隆显示的依赖倍性的亚硝基脲反应同样也不反映药物摄取的差异。
