Development of drug resistance in a murine mammary tumour.
The development of resistance to melphalan, cis-platinum and cyclophosphamide has been examined in the MT murine mammary carcinoma. A gradual decrease in therapeutic response was detected using growth delay and clonogenic cell survival during repeated drug treatment. A slow rate of resistance development, a gradual change in the slope of the dose-survival curves and the inability of 180 mg kg-1 cyclophosphamide to bring about a reduction in tumour response at a faster rate than 60 mg kg-1 cyclophosphamide suggest that resistance development was not due to the selection of a pre-existing highly drug resistant sub-population of tumour cells. Partial drug-resistance is proposed as one possible reason for the apparent inconsistency between these data and existing models of drug-resistance development. The drug-resistant lines were characterized for karyotype, DNA content and cell volume, but only the cyclophosphamide-resistant line showed any significant difference from the wild-type tumour. Cross-resistance studies revealed some inconsistencies with previous reports. Also, resistance to cyclophosphamide developed more quickly in the line which was resistant to melphalan, than in the wild-type tumour, despite the initial appearance of little cross-resistance. This increased rate of resistance development may be important in salvage chemotherapy.
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D002999:Clone Cells / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D066298:In Vitro Techniques; D007621:Karyotyping; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors
D004273:DNA, Neoplasm; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan