Evaluation of Drug Resistance in Cell Cultures by Differential Toxicity Tests2

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Abstract
Drug-resistant lines were obtained by cyclic exposure of clone strains of pig kidney cells to aminopterin, 2,6-diaminopurine, and allylglycine. Cultures of sensitive and resistant strains were assayed in graded concentrations of the corresponding inhibitor, and dose-response curves plotted from cell counts at 7 days. Resistant lines showed an increase in maximal levels of analogue tolerated without reduction in cell number, as well as by a rise in drug concentration required for 50 percent growth inhibition at 7 days. Drug resistance was specific for the analogue used to treat the parent strain, and cross-reactions to the other two inhibitors used were minimal or lacking.