Selection of Purine and Pyrimidine Nucleoside Analog Resistance in Mammalian Cells

  • John Morrow


Since its inception, somatic cell genetics has taken advantage of purine and pyrimidine analog resistance. In the initial stages of the development of this discipline variants resistant to these substances represented the most important and technically useful markers available in permanent cultured cell lines. Although in the past decade many new selective characters have been exploited, these substances are still widely used in genetic studies on somatic cells (Table I). Investigations in experimental mutagenesis (Clive et al., 1972), studies on DNA-mediated transformation (Scangos and Ruddle, 1981), gene mapping (McKusick, 1980), transport (Wohlhueter et al., 1978), somatic recombination (Rosenstraus and Chasin, 1978), and gene inactivation (Bradley, 1979) have taken advantage of these markers (Morrow, 1982).


Thymidine Kinase Chinese Hamster Cell Phosphoribosyl Transferase Pyrimidine Nucleoside Somatic Cell Genetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bradley, W. E. C., 1979, Reversible inactivation of autosomal alleles in Chinese hamster cells, J. Cell. Physiol. 101:325–340.PubMedCrossRefGoogle Scholar
  2. Chasin, L. A., 1974, Mutations affecting adenine phosphoribosyl transferase activity in Chinese hamster cells, Cell 2:37–41.PubMedCrossRefGoogle Scholar
  3. Chen, T., 1977, In Situ detection of mycoplasma contamination in cell cultures by fluorescent Hoeschst 33258 Stain, Exp. Cell Res. 104:255–262.PubMedCrossRefGoogle Scholar
  4. Clive, D., Flamm, W. G., Machesko, M. R., and Bernheim, N. J., 1972, A mutational assay system using the thymidine kinase locus in mouse lymphoma cells, Mutat. Res. 16:77–87.PubMedCrossRefGoogle Scholar
  5. Clive, D., Flamm, W. G., and Patterson, J. B., 1973, Specific locus mutational assay systems for mouse lymphoma cells, Appendix II in: Clinical Mutagens, Volume 3 (A. Hollander, ed.), pp. 100–103, Plenum Press, New York.Google Scholar
  6. Clive, D., Johnson, K., Spector, J., Batson, A., and Brown, M., 1979, Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system, Mutat. Res. 59:61–108.PubMedCrossRefGoogle Scholar
  7. DeMars, R., and Held, K., 1972, The spontaneous azaguanine-resistant mutants of diploid human fibroblasts, Humangenetik 16:87–110.PubMedCrossRefGoogle Scholar
  8. De Saint Vincent, B. R., and Buttin, G., 1979, Studies on 1-beta-D-arabinofuranosyl cytosine-resistant mutants of Chinese hamster fibroblasts: III. Joint resistance to arabinofurnanosyl cytosine and to excess thymidine: A semidominant manifestation of deoxycytidine triphosphate pool expansion, Somat. Cell Genet. 5:67–82.CrossRefGoogle Scholar
  9. Dickerman, L. H., and Tischfield, J., 1978, Comparative effets of adenine analogs upon metabolic cooperation between Chinese hamster cells with different levels of adenine phosphoribosyltransferase activity, Mutat. Res. 49:83–94.PubMedCrossRefGoogle Scholar
  10. Fox, M., and Radacic, M., 1978, Adaptational origin of some purine-analogue resistant phenotypes in cultured mammalian cells, Mutat. Res. 49:275–296.PubMedCrossRefGoogle Scholar
  11. Goldfarb, P. S. G., Slack, C., Subak-Sharpe, J., and Wright, E., 1974, Metabolic cooperation between cells in tissue culture, in: Symposia of the Society for Experimental Biology, Vol. 28, pp. 463–484, Cambridge University Press, London.Google Scholar
  12. Hakala, M. T., 1957, Prevention of toxicity of amethopterin for sarcoma 180 cells in tissue culture, Science 126:255–256.PubMedCrossRefGoogle Scholar
  13. Harris, M., 1964, Cell Culture and Somatic Variation, Holt, Rinehart and Winston, New York.Google Scholar
  14. Jha, K., and Ozer, H., 1976, Expression of transformation in cell hybrids. I. Isolation and application of density-inhibited Balb/3T3 cells deficient in hypoxanthine phosphoribosyl-transferase and resistant to ouabain, Somat. Cell Genet. 2:215–223.PubMedCrossRefGoogle Scholar
  15. Kit, S., Dubbs, D. R., Piekarski, L., and Hsu, T. C., 1963, Deletion of thymidine kinase activity from L cells resistant to bromodeoxyuridine Exp. Cell. Res. 31:297–312.CrossRefGoogle Scholar
  16. Littlefield, J. W., 1964a, Three degrees of guanylic acid-inosinic acid pyrophosphorylase deficiency in mouse fibroblasts, Nature 203:1142–1144.PubMedCrossRefGoogle Scholar
  17. Littlefield, J. W., 1964b, Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants, Science 145:709–710.PubMedCrossRefGoogle Scholar
  18. Lowy, I., Pellicer, A., Jackson, J., Sim, G., Silverstein, S., and Axel, R., 1980, Isolation of transforming DNA: Cloning the hamster aprt gene Cell 22:817–823.PubMedCrossRefGoogle Scholar
  19. McKusick, V. A., 1980, The anatomy of the human genome, J. Heredity 71:370–391.Google Scholar
  20. Medrano, L., and Green, H., 1974, A uridine kinase-deficient mutant of 3T3 and a selective method for cells containing the enzyme, Cell 1:23–26.CrossRefGoogle Scholar
  21. Morrow, J., 1970, Genetic analysis of azaguanine resistance in an established mouse cell line, Genetics 65:279–287.PubMedGoogle Scholar
  22. Morrow, J., 1975, On the relationship between spontaneous mutation rates in vivo and in vitro, Muta. Res. 33:367–372.CrossRefGoogle Scholar
  23. Morrow, J., 1977, Gene inactivation as a mechanism for the generation of variability in somatic cells cultivated in vitro, Mutat. Res. 44:391–400.PubMedCrossRefGoogle Scholar
  24. Morrow, J., 1982, Cell Genetics, Academic Press, New York.Google Scholar
  25. Morrow, J., Sammons, D., and Barron, E., 1980, Puromycin resistance in Chinese hamster cells: Genetic and biochemical studies of partially resistant, unstable clones, Mutat. Res. 69:333–346.PubMedCrossRefGoogle Scholar
  26. Patterson, D., 1980, Isolation and characterization of 5-fluorouracil resistant mutants of Chinese hamster ovary cells deficient in the activities of orotate phosphoribosyltransferase and orotidine 5-monophosphate decarboxylase, Somat. Cell Genet. 6:101–114.PubMedCrossRefGoogle Scholar
  27. Pellicer. A., Wigler, M., Axel, R., and Silverstein, S., 1978, The transfer and stable integration of the HSV thymidine kinase gene into mouse cells, Cell 14:133–141.PubMedCrossRefGoogle Scholar
  28. Peterson, A. R., Krahn, D. F., Peterson, H., Heidelberger, C., Bhuyan, B. K., and Li, L. H., 1976, The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine, Mutat. Res. 36:345–356.PubMedCrossRefGoogle Scholar
  29. Raskind, W., and Gartier, S., 1978, The relationship between induced mutation frequency and chromosome dosage in established mouse fibroblasts lines, Somat. Cell Genet. 4:491–506.PubMedCrossRefGoogle Scholar
  30. Reynolds, R., and Hetrick, F., 1969, Potential use of surface-active agents for controlling mycoplasma contamination in animal cell cultures, Appl. Microbiol. 17:405–411.PubMedGoogle Scholar
  31. Rosenstraus, M., and Chasin, L., 1978, Separation of linked markers in Chinese hamster cell hybrids: mitotic recombination is not involved, Genetics 90:735–760.PubMedGoogle Scholar
  32. Scangos, G., and Ruddle, F., 1981, Mechanisms and applications of DNA-mediated gene transfer in mammalian cells — A review, Gene 14:1–10.PubMedCrossRefGoogle Scholar
  33. Schneider, E. L., Stanbridge, E., and Epstein, C., 1974, Incorporation of 3H-Uridine and 3H-Uracil into RNA, Exp. Cell Res. 84:311–318.PubMedCrossRefGoogle Scholar
  34. Sharp, J. D., Capecchi, N., and Capecchi, M., 1973, Altered enzymes in drug resistant variants of mammalian tissue cultured cells, Proc. Natl. Acad. Sci. USA 70(11):3145–3149.PubMedCrossRefGoogle Scholar
  35. Shows, T. D., and Brown, J., 1975, Human X-linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids, Proc. Natl. Acad. Sci. USA 72:(6): 2125–2129.PubMedCrossRefGoogle Scholar
  36. Szybalski, W., and Szybalska, E., 1962, Drug sensitivity as a genetic marker for human cell lines, University of Michigan Medical Bulletin 28:277–293.PubMedGoogle Scholar
  37. Szybalski, W., Szybalska, E., and Ragni, G., 1962, Genetic studies with human cell lines, Natl. Cancer Inst. Monogr. 7:75–89.Google Scholar
  38. Ullman, B., Levinson, B., Hershfield, M., and Martin, D., 1981, A biochemical genetic study of the role of specific nucleoside kinases in deoxy-adenosine phosphorylation by cultured human cells, J. Biol. Chem. 256(2):848–852.PubMedGoogle Scholar
  39. Van Diggelen, O., Shin, S., and Phillips, D., 1977, Reduction in cellular tumorigenicity after mycoplasma infection and elimination of mycoplasma from infected cultures by passage in nude mice, Cancer Res. 37:2680–2687.PubMedGoogle Scholar
  40. Vesely, J., and Čihák, A. 1973, Resistance of mammalian tumor cells toward pyrimidine analogues, a review Oncology 28:204–226.PubMedCrossRefGoogle Scholar
  41. Westerveld, A., Visser, R., Freeke, M. A., and Bootsma, D., 1972, Evidence for linkage of PGK, HPRT, and GGPD in Chinese hamster cells studied by using a relationship between gene multiplicity and enzyme activity, Biochem. Genet. 7:33–40.PubMedCrossRefGoogle Scholar
  42. Wohlhueter, R., Marz, R., Graff, J., and Plagemann, P., 1978, A rapid-mixing technique to measure transport in suspended animal cells: Application to nucleoside transport in Novikoff rat hepatoma cells, in: Methods in Cell Biology, Volume 20 (David Prescott, ed.), Academic Press, New York, pp. 211–236.Google Scholar
  43. Wolpert, M., Damle, S., Brown, J., Sznycer, E., Agrawal, K., and Sartorelli, A., 1971, The role of phosphohydrolases in the mechanism of resistance of neoplastic cells to 6-thiopurines, Cancer Res. 31:1620–1626.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • John Morrow
    • 1
  1. 1.Department of BiochemistryTexas Tech University Helth Sciences CenterLubbockUSA

Personalised recommendations