Development of resistance to vincristine in a childhood rhabdomyosarcoma growing in immune-deprived mice.
A cell line of childhood rhabdomyosarcoma (RD) has been grown as a xenograft in immune-deprived mice. The tumor responded to vincristine (VCR), but not to vinblastine, doxorubicin or actinomycin D. The rate and frequency at which resistance developed from administration of VCR once weekly was investigated. Tumor growth could be inhibited for 6 weeks, after which time 11 or 16 xenografts grew progressively despite continued treatment. That this was a tumor-acquired resistance was confirmed by growing both parent and "resistant" lines in the same host. Under these conditions VCR completely inhibited growth of the parent tumor, but not growth of the resistant for 6 weeks, after which time 11 or 16 xenografts grew progressively despite continued treatment. That this was a tumor-acquired resistance was confirmed by growing both parent and "resistant" lines in the same host. Under these conditions VCR completely inhibited growth of the parent tumor, but not growth of the resistant for 6 weeks, after which time 11 or 16 xenografts grew progressively despite continued treatment. That this was a tumor-acquired resistance was confirmed by growing both parent and "resistant" lines in the same host. Under these conditions VCR completely inhibited growth of the parent tumor, but not growth of the resistant line. Continued passage of the resistant line for 10 months in mice either treated with VCR (1.5 mg/kg/wk) or untreated, demonstrated that resistance to VCR was stable in the absence of selection pressure. In addition, the VCR-resistant line acquired a stable change in karyotype with the addition of a number 9 chromosome and an additional, unknown marker.
D000818:Animals; D002648:Child; D003609:Dactinomycin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D007165:Immunosuppression Therapy; D007621:Karyotyping; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000235:genetics; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use*
D003609:Dactinomycin; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin