Hypoxanthine-guanine phosphoribosyltransferase deficiency: chemical agents selective for mutant or normal cultured fibroblasts in mixed and heterozygote cultures.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 68 ·No. 7 ·1971-07-00 ·Pages 1516-9

Fujimoto WY, Subak-Sharpe JH, Seegmiller JE

Abstract

Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyl-transferase (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.

MeSH Terms

Autoradiography Azaserine/pharmacology Cell Line/drug effects,enzymology Culture Techniques Fibroblasts/drug effects,enzymology Genetics, Medical Guanine Nucleotides Heterozygote Humans Hypoxanthines/metabolism Lesch-Nyhan Syndrome Mutation Pentosephosphates Selection, Genetic Skin Thioguanine/pharmacology Time Factors Transferases/analysis Tritium

Chemicals

Guanine Nucleotides Hypoxanthines Pentosephosphates Tritium Azaserine Transferases Thioguanine

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Fujimoto W Y

Subak-Sharpe J H

Seegmiller J E

References (23)

23 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.68.7.1516

Published

1971-07-00

Pages

1516-9

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC389230

Subset

External Links

PubMed source DOI: 10.1073/pnas.68.7.1516 PMC Full Text View journal details

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Hypoxanthine-guanine phosphoribosyltransferase deficiency: chemical agents selective for mutant or normal cultured fibroblasts in mixed and heterozygote cultures.

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