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Isolation and genetic characterization of human KB cell lines resistant to multiple drugs
Abstract:
Human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections. Most of these selection steps resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin; however, at the highest levels of colchicine resistance, increased cross-resistance to other drugs was not observed. There was no major change in protein synthesis or alteration in protein phosphorylation or [14C]glucosamine labeling patterns accompanying the development of multiple drug resistance as measured by analysis of metabolically labeled proteins on SDS gels. Cell-cell hybridization experiments showed that the colchicine-resistant and multiple drug-resistant phenotypes were incompletely dominant. In addition, colchicine resistance was found to segregate independently from resistance to other drugs in one somatic cell hybrid, suggesting that complex genetic loci are involved in the development of the multiple drug-resistant phenotype. These mutants should be useful for the study of the clinically important problem of multiple drug resistance in human cancer.
Insights
Researchers developed colchicine-resistant human KB cell lines exhibiting cross-resistance to various chemotherapy drugs. Genetic analysis suggests complex loci control this multiple drug resistance, offering insights into cancer treatment challenges.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Multiple drug resistance (MDR) is a significant challenge in cancer chemotherapy.
- Understanding the genetic and molecular basis of MDR is crucial for developing effective treatments.
Purpose of the Study:
- To isolate and characterize human cell lines with high-level colchicine resistance.
- To investigate the cross-resistance patterns and genetic basis of MDR in these cell lines.
Main Methods:
- Sequential single-step selection to generate colchicine-resistant KB cell lines.
- Analysis of protein synthesis, phosphorylation, and glycosylation patterns.
- Cell-cell hybridization experiments to assess dominance and segregation of resistance phenotypes.
Main Results:
- Isolated cell lines showed high-level colchicine resistance with varying cross-resistance to other anticancer drugs.
- No significant alterations in protein synthesis, phosphorylation, or glycosylation were observed.
- Colchicine resistance and MDR phenotypes were incompletely dominant and segregated independently in somatic cell hybrids, indicating complex genetic control.
Conclusions:
- The developed cell lines provide a valuable model for studying MDR in human cancer.
- The findings suggest that complex genetic loci are involved in the development of MDR.
- Further research into these genetic mechanisms could lead to strategies to overcome drug resistance in cancer therapy.