Advertisement

Prospects for Cellular Mutational Assays in Human Populations

  • Mortimer L. Mendelsohn
Part of the Basic Life Sciences book series

Abstract

Practical, sensitive, effective, human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis. When available, such assays should allow us to fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. We will be able to validate the role of somatic mutation in carcinogenesis, to identify environmental factors that affect human germ cells, to integrate the effects of complex mixtures and the environment in the human subject, and to identify people who are hypersusceptible to genetic injury. Human cellular mutational assays, particularly when combined with cytogenetic and heritable mutational tests, promise to play pivotal roles in estimating the risk from low-dose radiation and chemical exposures. These combined methods avoid extrapolations of dose and from species to species, and may be sensitive enough and credible enough to permit politically, socially and scientifically acceptable risk management.

Keywords

Somatic Mutation Single Amino Acid Substitution Lawrence Livermore National Laboratory Human Peripheral Blood Lymphocyte High Variant Frequency 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Albertini, R.J., 1982, Studies with T-lymphocytes: An approach to human mutagenicity monitoring, in: “Banbury Report 13, Indicators of Genotoxic Exposure,” pp. 393–412, B.A. Bridges, B.E. Butterworth, and I.B. Weinstein, eds., Cold Spring Harbor Lab.Google Scholar
  2. Albertini, R.J., Castle, K.L., and Borcherding, W.R., 1982, T-cell cloning to detect the mutant 6-thioguanine-resistant lymphocytes present in human peripheral blood, Proc. Natl. Acad. Sci. USA, 79:6617.PubMedCrossRefGoogle Scholar
  3. Amneus, H., Matsson, P., and Zetterberg, G., 1982, Human lymphocytes resistant to 6-thioguanine: Restrictions in the use of a test for somatic mutations arising in vivo studied by flow-cytometric enrichment of resistant cell nuclei, Mutat. Res., 106:163.PubMedCrossRefGoogle Scholar
  4. Ansari, A.A., Baig, M.A., and Mailing, H.V., 1980, In vivo germinal mutation detection with “monospecific” antibody against lactate dehydrogenase-x, Proc. Natl. Acad. Sci. USA, 77:7352.PubMedCrossRefGoogle Scholar
  5. Atwood K.C., and Petter, F.J., 1961, Erythrocyte automosaicism in some persons of known genotype, Science, 134:2100.PubMedCrossRefGoogle Scholar
  6. Bigbee, W.L., Branscomb, E.W., Weintraub, H.B., Papayannopoulou, Th., and Stamatoyannopoulos, G., 1981, Cell sorter immunofluorescence detection of human erythrocytes labeled in suspension with antibodies specific for hemoglobin S and C., J. Immunol. Methods, 45:117.PubMedCrossRefGoogle Scholar
  7. Bigbee, W.L., Langlois, R.G., Vanderlaan, M., and Jensen, R.H., 1984, Binding specificities of eight monoclonal antibodies to human glycophorin A: Studies using MCM and MkEn(UK) variant human erythrocytes and M- and MNV-type chimpanzee erythrocytes, J. Immunol. (in press).Google Scholar
  8. Bigbee, W.L., Vanderlaan, M., Fong, S.S.N., and Jensen, R.H., 1983, Monclonal antibodies specific for the M- and N-forms of human glycophorin A, Mol. Immunol., 20:1353.PubMedCrossRefGoogle Scholar
  9. Jensen, R.H., Bigbee, W.L., and Branscomb, E.W., 1984, Somatic mutations detected by immunofluorescence and flow cytometry, in: “Biological Dosimetry”, pp. 161–170, W. Eisert and M.L. Mendelsohn, eds., Springer-Verlag, Heidelberg.CrossRefGoogle Scholar
  10. Jones, I.M., Burkhart-Schultz, K., and Carrano, A.V., 1984, Cloning of thioguanine resistant lymphocytes for measurement of in vivo mutation in the mouse (in preparation).Google Scholar
  11. Morley, A.A., Cox, S., Wigmore, D., Seshadri, R., and Dempsey, J.L., 1982, Enumeration of thioguanine-resistant lymphocytes using autoradiography, Mutat. Res. 95:363.PubMedCrossRefGoogle Scholar
  12. Morley, A.A., Trainor, K.J., Seshadri, R., and Ryall, R.G., 1983, Measurement of in vivo mutations in human lymphocytes, Nature (London), 302:155.CrossRefGoogle Scholar
  13. Papayannopoulou, Th., Lira, G., McGuire, T.C., Ahern, V., Nute, P.E., and Stamatoyannopoulos, G., 1977, Use of specific fluorescent antibodies for the identification of hemoglobin C in erythrocytes, Am. J. Hematol., 2:105.PubMedCrossRefGoogle Scholar
  14. Papayannopoulou, Th, McGuire, T.C., Lim, G., Garzel, E., Nute, P.E., and Stamatoyannopoulos, G., 1976, Identification of haemoglobin S in red cells and normoblasts, using fluorescent anti-Hb S antibodies, Br. J. Haematol., 34:25.PubMedCrossRefGoogle Scholar
  15. Stamatoyannopoulos, G., Nute, P.E., Papayannopoulou, Th., McGuire T.C., Lim, G., Bunn, H.F., and Rucknagel, D., 1980, Development of a somatic mutation screening system using Hb mutants. IV. Successful detection of red cells containing the human frameshift mutants Hb Wayne and Hb Cranston using monospecific fluorescent antibodies, Am. J. Hum. Genet., 32:484.PubMedGoogle Scholar
  16. Strauss, G.H., and Albertini, R.J., 1979, Enumeration of 6-Thioguanine resistant peripheral blood lymphocytes in man as a potential test for somatic cell mutation arising in vivo, Mutat. Res., 61:353.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Mortimer L. Mendelsohn
    • 1
  1. 1.Biomedical Sciences DivisionLawrence Livermore National LaboratoryLivermoreUSA

Personalised recommendations