Peripheral Blood Lymphocytes as Indicator Cells for in vivo Mutation in Man

  • Gösta Zetterberg
Part of the Environmental Science Research book series (ESRH, volume 30)

Abstract

For the determination of the mutation rate of a single gene it is necessary to screen a very large number of the individual units chosen as testing objects. Single cell systems have been developed making possible the effective scoring of billions of cells in a short time. The mutants observed and counted are clones, originating from a single mutant cell. Most of the methods having microorganisms as testing objects use selective media in which only the mutants can grow out to colonies large enough to be scored by the naked eye. The same principles have been applied to mammalian cells, transformed to grow continuously, e.g., cell lines of Chinese hamster or humans. Results from such mutation tests are used for the risk evaluation of human exposure to genotoxic agents. However, the information gained in such tests about the genotoxic effects of a chemical in humans has limited value, mainly because human pharmacokinetic and metabolic factors are difficult to mimic. Therefore, there is great potential value in a mutation test performed with human cells constructed so that mutation can occur in vivo, the indicator cells can be withdrawn, and the mutant character can be developed in vitro.

Keywords

Psoriasis Sorting Pyrimidine Thymidine Purine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    K. C. Atwood, The presence of A2 erythrocytes T in Ax blood, Proc. Natl. Acad. Sci. USA, 44:1054– 1057 (1958).ADSCrossRefGoogle Scholar
  2. 2.
    K. C. Atwood and S. L. Scheinberg, Somatic variation in human erythrocyte antigens, J. Cell Comp. Phys., 52:97–123 (1958).CrossRefGoogle Scholar
  3. 3.
    H. E. Sutton, Monitoring of somatic mutations in human populations, in: Mutagenic Effects on Environmental Contaminants (E. H. Sutton and M. I. Harris, eds.), Academic Press, New York, pp. 121–128 (1972).Google Scholar
  4. 4.
    H. E. Sutton, Somatic cell mutations, in: Birth Defects; Proceedings 4th International Conference (A. G. Motulsky and W. Lenz, eds.), Exerpta Medica, Amsterdam, pp. 212–214 (1974).Google Scholar
  5. 5.
    T. Papayannopoulou, T. C. McGuire, G. Lim, E. Garzel, P. E. Nute, and G. Stamatoyannopoulos, Identification of haemoglobin S in red cells and normoblasts, using fluorescent anti-Hb S antibodies, Br. J. Haematol., 34:25–31 (1976).CrossRefGoogle Scholar
  6. 6.
    W. L. Bigbee, E. W. Branscomb, H. B. Weintraub, Th. Papayannopoulou, and G. Stamatoyannopoulos, Cell sorter immunofluorescence detection of human erythrocytes labeled in suspension with antibodies specific for hemoglobin S and C, J. Immunol. Methods, 45:117–127 (1981).CrossRefGoogle Scholar
  7. 7.
    G. H. Strauss and R. J. Albertini, 6-Thioguanine resistant lymphocytes in human peripheral blood, in: Progress in Genetic Toxicology (D. Scott, B. A. Bridges, and F. H. Sobels, eds.), Elsevier/North Holland, Amsterdam, pp. 327–334 (1977).Google Scholar
  8. 8.
    G. H. Strauss and R. J. Albertini, Enumeration of 6-thioguan- ine-resistant peripheral blood lymphocytes in man as a potential test for somatic cell mutations arisingin vivo, Mutat. Res., 61:353–379 (1979).CrossRefGoogle Scholar
  9. 9.
    H. J. Evans and Vijayalaxmi, Induction of 8-azaguanine resistance and sister chromatid exchange in human lymphocytes exposed to mitomycin C and X raysin vitro, Nature, 292:601–605 (1981).ADSCrossRefGoogle Scholar
  10. 10.
    H. Amn£us, P. Matsson, and G. Zetterberg, Human lymphocytes resistant to 6-thioguanine: Restrictions in the use of a test for somatic mutations arisingin vivostudied by flow-cytom- etric enrichment of resistant cell nuclei, Mutat. Res., 106: 163–178 (1982).CrossRefGoogle Scholar
  11. 11.
    C. T. Caskey and G. D. Kruh, The HPRT locus, Cell, 16:1–9 (1979).CrossRefGoogle Scholar
  12. 12.
    R. DeMars, Genetic studies of HGPRT-deficiency and the Lesch- Nyhan syndrome with cultured human cells, Fed. Proc., 30:944–955 (1971).Google Scholar
  13. 13.
    R. DeMars, Resistance of cultured human fibroblasts and other cells to purine and pyrimidine analogoues in relation to mutagenesis detection, Mutat. Res., 24:335–364 (1974).CrossRefGoogle Scholar
  14. 14.
    H. N. Kelley, Enzymology and biochemistry, A. HG-PRT deficiency in the Lesch-Nyhan syndrome and gout, Fed. Proc., 27:1047–1052 (1968).Google Scholar
  15. 15.
    P. Stutts and R. W. Brockman, A biochemical basis for resistance of L 1210 mouse leukeran to 6-thioguanin, Biochem. Pharmacol., 12:97–104 (1963).CrossRefGoogle Scholar
  16. 16.
    G. B. Elion and G. H. Hitchings, Metabolic basis for the ac¬tions of analogs of purines and pyrimidines, in: Advances in Chemotheraphy (A. Goldin, F. Hawkin, and R. J. Schnitzer, eds.), Vol. 2, pp. 91–97, Academic Press, New York (1965).Google Scholar
  17. 17.
    G. B. Elion, Biochemistry and pharmacology of purine analogs, Fed. Proc., 26:898–904 (1967).Google Scholar
  18. 18.
    R. P. Miech, R. E. Parks, Jr., J. H. Anderson, Jr., and A. C. Sartorelli, A hypothesis on the mechanism of action of 6-thio- guanine, Biochem. Pharmacol., 16:2222–2227 (1967).CrossRefGoogle Scholar
  19. 19.
    J. Arly-Nelson, J. W. Carpenter, L. M. Rose, and D. J. Adamson, Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine, Cancer Res., 35:2872–2878 (1975).Google Scholar
  20. 20.
    M. Lesch and W. L. Nyhan, A familial disorder or uric acid metabolism and control nervous system function, Am. J. Med., 36:561–570 (1964).CrossRefGoogle Scholar
  21. 21.
    J. E. Seegmiller, F. M. Rosenbloom, and W. N. Kelley, Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis, Science, 155:1682–1684 (1967).ADSCrossRefGoogle Scholar
  22. 22.
    C. H. M. M. de Bryun, Hypoxanthine-guanine phosphoribosyl- transferase deficiency, Human Genet., 31:127–150 (1976).CrossRefGoogle Scholar
  23. 23.
    L. B. Vogler, C. E. Grossi, and M. D. Cooper, Human lymphocyte subpopulations, Progress in Hematology, 11:1–45 (1979).Google Scholar
  24. 24.
    R. J. Albertini, E. F. Allen, A. S. Quinn, M. R. Albertini, Human somatic cell mutation:In vivovariant lymphocyte frequencies as determined by 6-thioguanine resistance, in: Population and Biological Aspects of Human Mutation (E. B. Hook and J. H. Porter, eds.), pp. 235–263, Academic Press, New York (1981).Google Scholar
  25. 25.
    R. P. Wagner and H. K. Mitchell, in: Genetics and Metabolism, 2nd ed., John Wiley and Sons, Inc., New York (1964).Google Scholar
  26. 26.
    . R. J. Albertini and W. R. Borcherding, Cloningin vitroof human 6-thioguanine resistant (TGr) peripheral blood lymphocytes (PBL’s) arisingin vivo, Abstract 13th Ann. Mtg. Environ. Mutagen Society, Environ. Mutag. (in press) (1982).Google Scholar
  27. 27.
    . R. J. Albertini, STudies with T-lymphocytes: An approach to human mutagenicity monitoring, in: Indicators of Genotoxic Exposure (B. A. Bridges, B. E. Butterworth, and I. B. Weinstein, eds.), Banbury Report, 13:393–412, Cold Spring Harbor Laboratory (1982).Google Scholar
  28. 28.
    G. H. S. Strauss, Direct mutagenicity testing: The development of a clonal assay to detect and quantitate mutant lymphocytes arising in vivo, in: Indicators of Genotoxic Exposure (B. A. Bridges, B. E. Butterworth, and I. B. Weinstein, eds.), Banbury Report, 13:423–441, Cold Spring Harbor Laboratory (1982).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Gösta Zetterberg
    • 1
  1. 1.Department of GeneticsUniversity of UppsalaUppsalaSweden

Personalised recommendations