Related Experiment Videos
[Characteristics of anthracycline-resistant strains of P388 leukemia]
Abstract:
Two strains of P388 murine leukemia with acquired resistance to rubomycin (P388/rm) and its nitroxyl derivative ruboxyl (P388/rx). The rubomycin resistance has been developed by the 14th generation and ruboxyl one-by the 8th generation. The growth kinetic patterns and the cell cycle time of the parent and resistant strains were similar. An increased tumourogenicity of both resistant strains cells was found. The resistance development was accompanied by the appearance of the additional chromosome materials, namely of homogeneously staining region (P388/rx) and of double chromatin bodies (P388/rm). The partial recovery of sensitivity to rubomycin occurred during 36 generations (1 year). Simultaneously the genetic markers have been lost. The recovery of sensitivity to ruboxyl in this period was not observed. The obtained resistant strains possessed the multidrug resistance: the cross resistance of P388/rm and P388/rx to actinomycin D, Vinca alkaloids and colchicine was shown.
Insights
Acquired resistance to rubomycin and ruboxyl in P388 leukemia cells led to increased tumourogenicity and multidrug resistance. Sensitivity partially recovered for rubomycin but not ruboxyl, with associated genetic marker loss.
Area of Science:
- * Pharmacology and Toxicology
- * Cancer Biology
- * Genetics
Context:
- * P388 murine leukemia models are utilized to study drug resistance mechanisms.
- * Acquired resistance to rubomycin and its derivative ruboxyl was developed over multiple generations.
- * Investigating the genetic and phenotypic changes associated with acquired drug resistance is crucial for understanding cancer progression and treatment failure.
Purpose:
- * To characterize the P388/rm and P388/rx cell lines with acquired resistance to rubomycin and ruboxyl, respectively.
- * To analyze the growth kinetics, cell cycle, tumourogenicity, and genetic alterations in resistant leukemia strains.
- * To assess the stability of acquired resistance and the potential for cross-resistance to other chemotherapeutic agents.
Summary:
- * Two resistant P388 murine leukemia strains, P388/rm and P388/rx, were developed. Resistant strains exhibited similar growth kinetics and cell cycle times but increased tumourogenicity compared to the parent strain.
- * Acquired resistance was associated with chromosomal abnormalities: homogeneously staining regions in P388/rx and double chromatin bodies in P388/rm.
- * Partial recovery of rubomycin sensitivity occurred after 36 generations with loss of genetic markers, while ruboxyl sensitivity did not recover. Both resistant strains displayed multidrug resistance, including cross-resistance to actinomycin D, Vinca alkaloids, and colchicine.
Impact:
- * Demonstrates the complex interplay between drug exposure, genetic instability, and the development of multidrug resistance in leukemia.
- * Highlights the potential for acquired resistance to alter cancer cell behavior, increasing tumourogenicity.
- * Provides insights into the mechanisms of resistance and cross-resistance, informing future therapeutic strategies for leukemia and other cancers.