Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: Chemical Agents Selective for Mutant or Normal Cultured Fibroblasts in Mixed and Heterozygote Cultures

• Published in: Proceedings of the National Academy of Sciences - PNAS 1971-07, Vol.68 (7), p.1516-1519
• Main Authors: Fujimoto, Wilfred Y., Subak-Sharpe, John H., Seegmiller, J. Edwin
• Format: Article
• Language: English
• Subjects: Autoradiography; Azaserine - pharmacology; Biological Sciences: Genetics; Cell Line - drug effects; Cell Line - enzymology; Cell lines; Culture Techniques; Cultured cells; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - enzymology; Flasks; Genetics, Medical; Guanine Nucleotides; Heterozygote; Heterozygotes; Humans; Hypoxanthines - metabolism; Hypoxia; Lesch-Nyhan Syndrome; Mutation; Nucleic acids; Nucleotides; Pentosephosphates; Purines; Selection, Genetic; Skin; Somatic cells; Thioguanine - pharmacology; Time Factors; Transferases - analysis; Tritium
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.68.7.1516

Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This deficiency makes possible the use of chemicals that select either for or against deficient variants in cultured fibroblasts. Two-way selection has been achieved by the use of 6-thioguanine, which selects for the deficient mutant, and azaserine, which selects to some extent for the normal allele in mixed cultures, as well as in cultures from heterozygotes. Theoretical considerations predict that the phenomenon of metabolic cooperation would tend to reinforce the former and to weaken the latter type of selection, and this is in accordance with the experimental findings.