Different clonal drug sensitivity of murine neuroblastoma cells in vivo

Four cloned murine neuroblastomas were implanted intramuscularly into the left thigh of adult A/Jax mice. Cyclophosphamide, cisplatin, adriamycin, imidazole carboxamide, and vincristine were administered intraperitoneally, in a dose of one third to one fourth of a median lethal dose, every week after the implantation until all the mice died. The effects of continuous long-term chemotherapy, particularly on clonal differences, were then assessed. Cyclophosphamide was most effective for four murine neuroblastomas, and cisplatin was the next most effective drug. Cisplatin was not effective in the NS-20 cell line, a cholinergic cloned neuroblastoma. The C 1300 cell line (wild type) was tolerant to adriamycin, imidazole carboxamide, and vincristine. The N-18 cell line (an inactive clone) exhibited tolerance of adriamycin and imidazole carboxamide. In the N1E-115 cell line, an adrenergic clone, tumor growth was inhibited by all the drugs given. We conclude from this study that drug sensitivity differs with the clone, and that there are clones resistant to each drug.