1887

Abstract

SUMMARY: Under conditions of limited-adenine supplementation, 8-azaguanine is a potent inhibitor of purine auxotrophic strains of . It is relatively ineffective in prototrophic strains. Spontaneous and u.v.-light-induced mutants, resistant to 8-azaguanine, were obtained in a strain carrying the ad-2, ad-3A, and ad-3B markers. The resistant mutants grew in the presence of 200 8-azaguanine and 2·0 g adenine sulphate/ml medium. Inhibition of the sensitive strain is virtually complete under these conditions. Higher adenine sulphate concentrations prevent inhibition of the sensitive strain by 8-azaguanine. Resistance of the new mutants to 8-azaguanine was demonstrated by growth-tube experiments and by plating efficiencies in the presence and in the absence of the inhibitor. Growth-tube experiments were also used to study the reversal of 8-azaguanine induced inhibition by adenine sulphate. The resistance markers in the five strains studied were assigned to linkage group III. The locus designation was given to the resistance marker in a selected mutant of spontaneous origin. Resistance to 8-azaguanine is stable in the presence and in the absence of the inhibitor. In heterokaryons, 8-azaguanine resistance is recessive.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-83-2-319
1974-08-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/83/2/mic-83-2-319.html?itemId=/content/journal/micro/10.1099/00221287-83-2-319&mimeType=html&fmt=ahah

References

  1. Balis M. E. 1968; Antagonists and nucleic acids. In Frontiers of Biology 10 Amsterdam: North Holland Publishing;
    [Google Scholar]
  2. Bedair B. J., Fuerst R. 1961; Adaptability of Neurospora to 6-diazo-5-oxo-l-norleucine and related inhibiting agents. Antimicrobial Agents and Chemotherapy 1:260–267
    [Google Scholar]
  3. Brockman R. W., Sparks C, Hutachinson D., Skipper H. E. 1959; A mechanism of resistance to 8-azaguanine. I. Microbial studies on the metabolism of purines and 8-azapurines. Cancer Research 19:177–188
    [Google Scholar]
  4. Chu E. H. Y. 1971; Mammalian cell genetics. III. Characterization of X-ray-induced forward mutations in Chinese hamster cell cultures. Mutation Research 11:23–34
    [Google Scholar]
  5. Chu E. H. Y., Brimer P., Jacobson K. B., Merriam E. V. 1969; Mammalian cell genetics. I. Selection and characterization of mutations auxotrophic for l-glutamine or resistant to 8-azaguanine in Chinese hamster cells in vitro . Genetics 62:359–377
    [Google Scholar]
  6. Chu E. H. Y., Malling H. V. 1968; Mammalian cell genetics. II. Chemical induction of specific locus mutations. Proceedings of the National Academy of sciences of the United States of America 61:1306–1312
    [Google Scholar]
  7. Fairley J. L., Loring H. S. 1949; Growth-promoting activities of guanine, guanosine, guanylic acid, and xanthine for a purine-deficient strain of Neurospora . Journal of Biological Chemistry 177:451–459
    [Google Scholar]
  8. Harbers E., Domagk G., Muller W. 1968 Introduction to Nucleic Acids -Chemistry, Biochemistry and Functions pp 294–328 New York: Reinhold Book Co;
    [Google Scholar]
  9. Heslot H., Nagy M., Whitehead E. 1966; Recherches genetiques et biochimiques sur la primiere enzyme de la biosynthesis des purines chez le schizosaccharomyces pombe . Comptes rendus hebdomadaire des séances de l’ Académic des sciences 263:D57–58
    [Google Scholar]
  10. Hoffmann G. R., Malling H. V. 1974; Detection of 8-azaguanine resistant mutants in a Neurospora heterokaryon. Fifth Annual Environmental Mutagen Society Meeting Abstracts; Washington D.C: 8-11 March 1974
    [Google Scholar]
  11. Hoffmann G. R., Malling H. V., Mitchell T. J. 1973; Genetics of 5-fluorodeoxyuridine resistant mutants of Neurospora crassa . Canadian Journal of Genetics and Cytology 15:831–844
    [Google Scholar]
  12. Horowitz N. H., Beadle G. W. 1943; A microbiological method for the determination of choline by use of a mutant of Neurospora . Journal of Biological Chemistry 150:325–333
    [Google Scholar]
  13. Jagger J. 1961; A small and inexpensive UV dose-rate meter useful in biological experiments. Radiation Research 14:394–403
    [Google Scholar]
  14. Jha K. K. 1971; Genes conferring resistance to 8-azaadenine in Neurospora crassa and the variability of resistant alleles in the aza-1 locus with respect to purines. Molecular and General Genetics 114:156–167
    [Google Scholar]
  15. Kalle G. P., Gots J. S. 1961; Alterations in purine nucleotide pyrophosphorylases and resistance to purine analogues. Biochimica et biophysica acta 53:166–173
    [Google Scholar]
  16. Mahadevan P. R., Bhagwat A. S. 1969; Inhibition of protein synthesis in Neurospora crassa by 8-azaguanine. Indian Journal of Biochemistry 6:169–174
    [Google Scholar]
  17. Morpurgo G. 1962; A new method of estimating forward mutation in fungi: resistance to 8-azaguanine and p-fluorophenylalanine. scientific Reports of the Instituto superiore di Sanitá 2:9–12
    [Google Scholar]
  18. Perevoschchikova K. A. 1969; Effect of 8-azaguanine on nucleic acid and protein synthesis in Ehrlich ascites Cancer cells in mice and in rat liver. Cancer Chemotherapy Abstracts 10:108
    [Google Scholar]
  19. Perkins D. D., Newmeyer D., Taylor C. W., Bennett D. C. 1969; New markers and map sequences in Neurospora crassa, with a description of mapping by duplication coverage, and of multiple translocation stocks for testing linkage. Genetica 40:247–278
    [Google Scholar]
  20. Pourquie J. 1970; Antagonism by adenine in the nutrition of schizosaccharomyces pombe mutants. Inhibition at the level of guanine uptake. Biochimica et biophysica acta 209:269–277
    [Google Scholar]
  21. Rode A., Bayen M. 1972; Action de la 8-azaguanine sur la division cellulaire de Chlorella pyrenoidosa. 1. Inhibition selective de la synthese de l’ADN nucleare. Planta 102:237–246
    [Google Scholar]
  22. Roy-Burman P. 1970; Analogues of nucleic acid components - mechanisms of action. In Recent Results in Cancer Research 25 New York: Springer-Verlag;
    [Google Scholar]
  23. De Serres F. J., Malling H. V. 1971; Measurement of recessive lethal damage over the entire genome and at two specific loci in the ad-3 region of a two-component heterokaryon of Neurospora crassa . In Chemical Mutagens: Principles and Methods for Their Detection 2 pp 311–342 Hollaender A. Edited by New York: Plenum Press;
    [Google Scholar]
  24. Shiio I., Ishii K. 1971; Genetically altered repression pattern of purine nucleotide synthesizing enzymes and inosine production in 8-azaguanine resistant mutants of Bacillus subtilis . Journal of Biochemistry 69:339–347
    [Google Scholar]
  25. Szybalski W. 1958; Resistance to 8-azaguanine, a selective marker for a human cell line. Microbial Genetics Bulletin 16:30
    [Google Scholar]
  26. Szybalski W., Smith M. J. 1959; Genetics of human cell lines. I. 8-Azaguanine resistance, a selective ‘single-step’ marker. Proceedings of the Society for Experimental Biology and Medicine 101:662–666
    [Google Scholar]
  27. Szybalski W., Szybalska E.H, Ragni G. 1962; Genetic studies with human cell lines. National Cancer Institute Monographs 7:75–89
    [Google Scholar]
  28. Westergaard M., Mitchell H. K. 1947; Neurospora. V. A synthetic medium favoring sexual reproduction. American Journal of Botany 34:573–577
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-83-2-319
Loading
/content/journal/micro/10.1099/00221287-83-2-319
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error