Population dynamics of purine and pyrimidine analog sensitive and resistant mammalian cells grown in culture.

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Abstract The population dynamics of purine analog resistance have been studied. Two types of reconstruction experiments were performed: cloning numbers of azaguanine resistant, BUdR resistant, and sensitive cells were plated in the presence of a large number of the opposite genotype, which were made to act as a feeder layer by inactivating them with either the appropriate analog or the reverse selective HAT medium. These experiments demonstrate that there is no significant metabolic cooperation between drug resistant and drug sensitive cells, with the exception of BUdR sensitive cells, which at high densities inhibit the cloning ability of BUdR resistant cells in the presence of the drug. Thus the purine analog resistance system can be used for obtaining quantitative data concerning such parameters as mutation and selection, while at high cell densities the pyrimidine analog system appears to be unsatisfactory.——A second series of experiments indicates that, in artificial mixtures of sensitive and resistant cells grown in standard medium, the resistant cells are at a selective disadvantage and will be reduced eventually to the frequency which is observed in wild type populations.