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• W2046671456 endingPage "2168" @default.
• W2046671456 startingPage "2159" @default.
• W2046671456 abstract "The cross-resistance patterns of single- and two-step mutants of HeLa cells resistant to SC4453 (a digoxin analog) and digoxin, which involve specific alteration in Na+, K+-ATPase towards numerous other compounds, have been examined. The mutants exhibited increased resistance to all of the steroidal compounds known to elicit a digitalis-like positive inotropic response (viz. various cardiac glycosides and their genins, erythrophleum alkaloid cassaine), but they showed no cross-resistance to any of a large number of other compounds which do not show cardiac glycoside (CG)-like biological activity. Based on the above characteristics of the mutants, a new cross-resistance assay for identifying compounds that show CG-like activity has been developed. In this assay, a sample is considered to possess CG-like activity if, in comparison to the parental HeLa cells, the CGR mutants exhibit increased resistance to it. From the known D10 value (drug concentration which reduces cloning efficiency of cells to 10%) of the drug for HeLa cells and the sample dilution necessary to produce equivalent cytotoxicity, the concentration of CGs in a given sample can be estimated. In blind studies the assay correctly identified all of the samples containing CGs; none of the other samples which lacked such activity tested positive. In the blind studies the assay also provided a good estimate of the concentration of CGs (+/- 50% of the actual concentration) that was not affected by the presence of either serum components or a 20-fold excess of various steroidal compounds known to interfere in other assays. In view of the high specificity of the present assay for CG-like compounds, it should prove very useful in establishing/characterizing the presence of such activity in various biological (namely endogenous digitalis-like substances) and other samples." @default.
• W2046671456 created "2016-06-24" @default.
• W2046671456 creator A5059172820 @default.
• W2046671456 creator A5077155083 @default.
• W2046671456 creator A5085988586 @default.
• W2046671456 date "1989-07-01" @default.
• W2046671456 modified "2023-09-25" @default.
• W2046671456 title "Development of a specific assay for cardiac glycoside-like compounds based on cross-resistance of human cell mutants" @default.
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• W2046671456 doi "https://doi.org/10.1016/0006-2952(89)90071-3" @default.
• W2046671456 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/2735954" @default.
• W2046671456 hasPublicationYear "1989" @default.
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