Abstract
The central premise of genetic toxicology is that environmental agents are responsible for genetic changes in man. This premise has not been tested and we thus have not confirmed if mutations in the population are predominantly spontaneous or environmentally induced. We propose in this paper a method that would permit us to discriminate between spontaneous and induced mutations in cells isolated from a population and thus diagnose the major mutagenic stimuli in humans.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
W. G. Thilly, P.-M. Leong, and T. R. Skopek, Potential of mutational spectra for diagnosing the cause of genetic change in human cell populations, in: Banbury Report 14 Indicators of Genotoxic Exposure in Man and Animals, Proceedings: Banbury Conference, April 1982 (in press).
S. Benzer, On the topography of the genetic fine structure, Proc. Natl. Acad. Sci. (U.S.A.), 47:403–415 (1961).
R. S. Gupta and L. Siminovitch, Mutants of CHO cells resistant to protein synthesis inhibitors, cryptopleurine, and tylocrebine, Genetic and biochemical evidence for common site of action of emetine, cryptopleurine, tylocrebine, and tubulosine, Biochemistry, 16:3209–3214 (1977).
M. Caboche and P. Mulsant, Selection and preliminary characterization of cycloleucine-resistant CHO cells affected in methionine metabolism, Som. Cell Genetics, 4:407–421 (1978).
R. S. Gupta and L. Siminovitch, Genetic markers for quantitative mutagenesis studies in CHO cells, Characteristics of some recently developed selection systems, Mut. Res., 69:113–129 (1980).
C. D. Whitfield, B. Buchsbaum, R. Bostedor, E. H. Y. Chu, Inverse relationship between glactokinase activity and 2-deoxy- galactose resistance in Chinese hamster ovary cells, Som. Cell Genetics, 4:699–713 (1978).
C. L. Crespi, The temporal induction of 6-thioguanine and ouabain resistance in synchronous Chinese hamster ovary cells by 5-bromo-2-deoxyuridine and ethyl methanesulfonate, M.S. Thesis, Department of Nutrition and Food Science, Massachusetts Institute of Technology (1979).
R. S. Gupta and L. Siminovitch, Genetic and biochemical characterization of mutants of CHO cells resistant to the protein synthesis inhibitor Trichodermin, Som. Cell Genetics, 4:355–374 (1978).
H. E. Lagarde and L. Siminovitch, Studies on CHO mutants showing multiple cross resistance to oxidative phosphorylation inhibitors, Som. Cell Genetics, 5:847–871 (1979).
C. E. Campbell and R. G. Warton, Evidence obtained by induced mutation frequency analysis for functional hemizygosity at emt locus in CHO cells, Som. Cell Genetics, 5:51–75 (1979).
W. G. Thilly, J. G. DeLuca, E. E. Furth, H. Hoppe, D. A. Kaden, J. J. Krolewski, H. L. Liber, T. R. Skopek, S. A. Slapikoff,R. J. Tizard, and B. W. Penman, Gene locus mutation assays in diploid human lymphoblast lines, in: Chemical Mutagens, Vol. 6 (F. J. de Serres and A. Hollaender, eds.), pp. 331–361 (1980).
T. W. Doyle and W. T. Bradner, Trichothecanes, Anticancer agents based on natural product models, p. 43 (1980).
S. Pestka, Inhibitors of ribosome functions, Ann. Review of Microbiology, 25: 487 (1971).
J. M. Clark, Jr., Gougerotin, Antibiotics, Vol. 1 (D. Gottlieb and P. D. Shar, eds.), Springer-Verlag, New York, p. 278 (1967).
M. Caloche and J. P. Bachellerie, RNA methylation and control of eukaryotic RNA biosynthesis, Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation, Eur. J. Biochem., 74: 19 (1977).
A. DiMarco, Daunomycin and related antibiotics, Antibiotics, Vol. 1 (D. Gottlieb and P. D. Shar, eds.), Springer-Verlag, New York, p. 190 (1967).
E. Egyhezi, A tentative initiation inhibitor of chromosomal heterogeneous RNA synthesis, J. Mol. Biol., 84: 173 (1974).
L. Wilson, J. R. Bamburg, S. B. Mizel, L. M. Grishan, and K. M. Greswell, Interaction of drugs with microtubule proteins, Fed. Proc., 33(2) –158 (1974).
T. Reichstein and H. Reich, The chemistry of steroids, Ann. Review of Biochemistry, 15:155, 1946: 403 (1977).
A. C. Guyton, Textbook of Medical Physiology, Fourth Edition, Part II, Blood Cells, Immunity, and Blood Clotting, W. B. Saunders Co., Philadelphia, pp. 98–146 (1971).
R. J. Albertini and R. B. Wayne, Cloningin vitroof human 6-thioguanine resistance (6TGR) peripheral blood lymphocytes (PBL’s) arisingin vivo, Program and Abstracts, 13th Annual Meeting, Environmental Mutagen Society, Environmental Mutagen Society, Washington, D.C., p. 134 (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Plenum Press, New York
About this chapter
Cite this chapter
Skopek, T.R., Leong, PM., Thilly, W.G. (1984). Discrimination between Spontaneous and Induced Mutations in Human Cell Populations by use of Mutational Spectra. In: de Serres, F.J., Pero, R.W. (eds) Individual Susceptibility to Genotoxic Agents in the Human Population. Environmental Science Research, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2765-3_16
Download citation
DOI: https://doi.org/10.1007/978-1-4613-2765-3_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-9709-3
Online ISBN: 978-1-4613-2765-3
eBook Packages: Springer Book Archive