Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1972 Oct;72(2):239–252. doi: 10.1093/genetics/72.2.239

8-Azaguanine Resistance in Mammalian Cells I. Hypoxanthine-Guanine Phosphoribosyltransferase

F D Gillin 1, D J Roufa 1, A L Beaudet 1, C T Caskey 1
PMCID: PMC1212824  PMID: 4345996

Abstract

Chinese hamster cells were treated with ethyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine, and mutants resistant to 8-azaguanine were selected and characterized. Hypoxanthine-guanine phosphoribosyltransferase activity of sixteen mutants is extremely negative, making them suitable for reversion to HGPRTase+. Ten of the extremely negative mutants revert at a frequency higher than 10-7 suggesting their point mutational character. The remaining mutants have demonstrable HGPRTase activity and are not useful for reversion analysis. Five of these mutants have < 2% HGPRTase and are presumably also HGPRTase point mutants. The remaining 14 mutants utilize exogenous hypoxanthine for nucleic acid synthesis poorly, and possess 20–150% of wild-type HGPRTase activity in in vitro. Their mechanism of 8-azaguanine resistance is not yet defined.

Full Text

The Full Text of this article is available as a PDF (847.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ATKINSON M. R., MURRAY A. W. INHIBITION BY 6-MERCAPTOPURINE OF PURINE PHOSPHORIBOSYLTRANSFERASES FROM EHRLICH ASCITES-TUMOUR CELLS THAT ARE RESISTANT TO THE DRUG. Biochem J. 1965 Jan;94:71–74. doi: 10.1042/bj0940071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CASKEY C. T., ASHTON D. M., WYNGAARDEN J. B. THE ENZYMOLOGY OF FEEDBACK INHIBITION OF GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE AMIDOTRANSFERASE BY PURINE RIBONUCLEOTIDES. J Biol Chem. 1964 Aug;239:2570–2579. [PubMed] [Google Scholar]
  3. Henderson J. F., Caldwell I. C., Paterson A. R. Decreased feedback inhibition in a 6-(methylmercapto)purine ribonucleoside-resistant tumor. Cancer Res. 1967 Oct;27(10):1773–1778. [PubMed] [Google Scholar]
  4. Henderson J. F., Kelley W. N., Rosenbloom F. M., Seegmiller J. E. Inheritance of purine phosphoribosyltransferases in man. Am J Hum Genet. 1969 Jan;21(1):61–70. [PMC free article] [PubMed] [Google Scholar]
  5. Kelley W. N., Meade J. C. Studies on hypoxanthine-guanine phosphoribosyltransferase in fibroblasts from patients with the Lesch-Nyhan syndrome. Evidence for genetic heterogeneity. J Biol Chem. 1971 May 10;246(9):2953–2958. [PubMed] [Google Scholar]
  6. MCCOLLISTER R. J., GILBERT W. R., Jr, ASHTON D. M., WYNGAARDEN J. B. PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES. J Biol Chem. 1964 May;239:1560–1563. [PubMed] [Google Scholar]
  7. Murray A. W. The biological significance of purine salvage. Annu Rev Biochem. 1971;40:811–826. doi: 10.1146/annurev.bi.40.070171.004115. [DOI] [PubMed] [Google Scholar]
  8. Nagy M. Regulation of the biosynthesis of purine nucleotides in Schizosaccharomyces pombe. I. Properties of the phosphoribosylpyrophosphate: glutamine amidotransferase of the wild strain and of a mutant desensitized towards feedback modifiers. Biochim Biophys Acta. 1970 Mar 18;198(3):471–481. doi: 10.1016/0005-2744(70)90125-7. [DOI] [PubMed] [Google Scholar]
  9. SUBAK-SHARPE H. BIOCHEMICALLY MARKED VARIANTS OF THE SYRIAN HAMSTER FIBROBLAST CELL LINE BHK21 AND ITS DERIVATIVES. Exp Cell Res. 1965 Apr;38:106–119. doi: 10.1016/0014-4827(65)90432-5. [DOI] [PubMed] [Google Scholar]
  10. Sherman F., Stewart J. W., Parker J. H., Putterman G. J., Agrawal B. B., Margoliash E. The relationship of gene structure and protein structure of iso-I-cytochrome c from yeast. Symp Soc Exp Biol. 1970;24:85–107. [PubMed] [Google Scholar]
  11. Thakar J. H., Kalle G. P. Defective guanine uptake in an 8-azaguanine-resistant mutant of Salmonella typhimurium. J Bacteriol. 1968 Feb;95(2):458–464. doi: 10.1128/jb.95.2.458-464.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. WYNGAARDEN J. B., ASHTON D. M. The regulation of activity of phosphoribosyl-pyrophosphate amidotransferase by purine ribonacleotides: a potential feedback control of purine biosyntoesis. J Biol Chem. 1959 Jun;234(6):1492–1496. [PubMed] [Google Scholar]
  13. Whitfield H. J., Jr, Martin R. G., Ames B. N. Classification of aminotransferase (C gene) mutants in the histidine operon. J Mol Biol. 1966 Nov 14;21(2):335–355. doi: 10.1016/0022-2836(66)90103-3. [DOI] [PubMed] [Google Scholar]
  14. Yanofsky C., Ito J., Horn V. Amino acid replacements and the genetic code. Cold Spring Harb Symp Quant Biol. 1966;31:151–162. doi: 10.1101/sqb.1966.031.01.023. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES