Frondoza C G, DiSanto J P, Humphrey R L
Oncology Center, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Hybridoma. 1988 Aug;7(4):397-405. doi: 10.1089/hyb.1988.7.397.
We have analyzed the expression of cyclophosphamide (CY) resistance in somatic cell hybrids of mouse LPC-1/CY-R plasmacytoma and P3-X63-Ag8.653 (Ag8) myeloma cells. LPC-1/CY-R tumor is resistant to curative doses (60-250 mg/kg body weight) of CY. The median survival time (MST) of drug treated LPC-1/CY-R tumor bearing mice is 25 days, similar to that of untreated mice. LPC-1/CY-R tumor cells secrete an IgG 2a kappa M component and do not survive in tissue culture. Ag8 tumor cells are CY sensitive, are selected out in hypoxanthine-aminopterin-thymidine (HAT) media and do not secrete any immunoglobulin. Hybrids formed between these two cell lines survived in HAT and secreted IgG 2a kappa. Hybrid cells exhibited greater ploidy than that of their parents and contained the metacentric marker chromosome of the Ag8 cell line. Hybrid cells exhibited the same growth characteristics in BALB/c mice as that of their LPC-1/CY-R parent and were resistant to curative doses of CY. These studies demonstrate that, CY resistance is a somatic cell dominant trait which can be transferred to daughter cells via somatic cell hybridization. Availability of somatic cell hybrids produced between CY sensitive and resistant tumor cells may provide useful tools to study the biochemical nature and the somatic cell genetics of this drug resistant trait.
我们分析了小鼠LPC-1/CY-R浆细胞瘤与P3-X63-Ag8.653（Ag8）骨髓瘤细胞的体细胞杂种中对环磷酰胺（CY）的抗性表达。LPC-1/CY-R肿瘤对治疗剂量（60 - 250 mg/kg体重）的CY具有抗性。经药物处理的荷LPC-1/CY-R肿瘤小鼠的中位生存时间（MST）为25天，与未处理小鼠相似。LPC-1/CY-R肿瘤细胞分泌一种IgG 2a κ M成分，且在组织培养中不能存活。Ag8肿瘤细胞对CY敏感，可在次黄嘌呤-氨基蝶呤-胸腺嘧啶核苷（HAT）培养基中筛选出来，且不分泌任何免疫球蛋白。这两种细胞系之间形成的杂种在HAT中存活并分泌IgG 2a κ。杂种细胞的倍性比其亲本更高，并含有Ag8细胞系的中着丝粒标记染色体。杂种细胞在BALB/c小鼠中的生长特性与其LPC-1/CY-R亲本相同，且对治疗剂量的CY具有抗性。这些研究表明，CY抗性是一种体细胞显性性状，可通过体细胞杂交传递给子代细胞。CY敏感和抗性肿瘤细胞之间产生的体细胞杂种可能为研究这种耐药性状的生化本质和体细胞遗传学提供有用的工具。
