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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 develo...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
1985
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977285/ https://www.ncbi.nlm.nih.gov/pubmed/4074637 |
Sumario: | 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. |
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