This study demonstrates the feasibility of transforming mouse cells deficient in adenine phosphoribosyltransferase (aprt) to the aprt⁺ phenotype using DNA-mediated gene transfer. The researchers used unfractionated high molecular weight genomic DNA from Chinese hamster, human, and mouse cells, as well as restriction endonuclease-digested DNA from rabbit liver. Transformation frequency was between 1 and 10 colonies per 10⁸ cells per 20 μg of donor DNA. Transformants displayed donor-derived enzymatic activity, as shown by isoelectric focusing of cytoplasmic extracts. These transformants were divided into two classes: those that were phenotypically stable in the absence of selective pressure and those that were phenotypically unstable. DNA-mediated gene transfer, previously used in prokaryotes, has now been extended to eukaryotes. The study shows that the aprt gene can be transferred to mutant cells lacking this enzyme. Transformants express aprt activity with characteristics of the organism from which the transforming DNA was derived. These results, combined with previous findings, demonstrate that DNA-mediated gene transfer in animal cells can serve as a bioassay for dominant-acting genes present at concentrations of one part per haploid genome. The method used to transfer the tk and aprt genes can be applied to any gene for which appropriate selective conditions and recipient cells exist. The researchers have successfully transferred the gene coding for a methotrexate-resistant folate reductase to wild-type cells. DNA-mediated gene transfer provides a unique bioassay for gene function and a method for gene isolation. The study highlights the potential of this technique for understanding complex cellular phenotypes in eukaryotic cells. The results indicate that DNA-mediated gene transfer is a powerful tool for genetic research.This study demonstrates the feasibility of transforming mouse cells deficient in adenine phosphoribosyltransferase (aprt) to the aprt⁺ phenotype using DNA-mediated gene transfer. The researchers used unfractionated high molecular weight genomic DNA from Chinese hamster, human, and mouse cells, as well as restriction endonuclease-digested DNA from rabbit liver. Transformation frequency was between 1 and 10 colonies per 10⁸ cells per 20 μg of donor DNA. Transformants displayed donor-derived enzymatic activity, as shown by isoelectric focusing of cytoplasmic extracts. These transformants were divided into two classes: those that were phenotypically stable in the absence of selective pressure and those that were phenotypically unstable. DNA-mediated gene transfer, previously used in prokaryotes, has now been extended to eukaryotes. The study shows that the aprt gene can be transferred to mutant cells lacking this enzyme. Transformants express aprt activity with characteristics of the organism from which the transforming DNA was derived. These results, combined with previous findings, demonstrate that DNA-mediated gene transfer in animal cells can serve as a bioassay for dominant-acting genes present at concentrations of one part per haploid genome. The method used to transfer the tk and aprt genes can be applied to any gene for which appropriate selective conditions and recipient cells exist. The researchers have successfully transferred the gene coding for a methotrexate-resistant folate reductase to wild-type cells. DNA-mediated gene transfer provides a unique bioassay for gene function and a method for gene isolation. The study highlights the potential of this technique for understanding complex cellular phenotypes in eukaryotic cells. The results indicate that DNA-mediated gene transfer is a powerful tool for genetic research.