Fundamentals of Genetic Toxicology

  • David J. Brusick
Chapter

Abstract

The purpose of this chapter is to describe the genetic background and terminology essential for an understanding of genetic toxicology. It is necessary to appreciate the basic structure of the target molecule, DNA, and to understand how it operates, since the types of molecular lesions that chemicals induce in this molecule and the genetic effects that they generate are intimately tied to the structure and function of this molecule. Because of the unique position held by DNA in maintaining and processing cellular information, intrinsic capacity for self-repair appears to have evolved simultaneously with the environmental adaptation of this molecule. Repair processes are also believed to influence the kinetics of mutation induction by preventing many chemically induced lesions from becoming fixed as permanent alterations.

Keywords

Sister Chromatid Exchange Mutation Induction Nucleotide Pair Chromatid Break Genetic Toxicology 
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.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ad Hoc Committee of The Environmental Mutagen Society and The Institute for Medical Research: Chromosome methodologies in mutation testing. Toxicol. Appl. Pharmacol. 22: 269–275, 1972.CrossRefGoogle Scholar
  2. 2.
    Ames, B. N., and Whitfield, H. J.: Frameshift mutagenesis in Salmonella. Cold Spring Harbor Symp. Quant. Biol. 31: 189–201, 1966.CrossRefGoogle Scholar
  3. 3.
    Badr, F. M., and Badr, R. S.: Studies on the mutagenic effect of contraceptive drugs. I. Induction of dominant lethal mutations in female mice. Mutat. Res. 26: 529, 1974.PubMedCrossRefGoogle Scholar
  4. 4.
    Benzer, S.: Fine structure of a genetic region in bacteriophage. In Papers on Genetics: A Book of Readings (Louis Levine, ed.), C. V. Mosby, St. Louis, pp. 287–294, 1971.Google Scholar
  5. 5.
    Cattanach, B. M.: Control of chromosome inactivation. In Annual Review of Genetics, Vol. 9 (H. L. Roman, ed.), Annual Reviews, Palo Alto, Calif., pp. 1–18, 1975.Google Scholar
  6. 6.
    Hart, R. W., and Setlow, R. B.: Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc. Natl. Acad. Sci. U.S.A. 71 (6): 2169–2173, 1974.PubMedCrossRefGoogle Scholar
  7. 7.
    Heddle, J.: A rapid in vitro test for chromosomal damage. Mutat. Res. 18: 187, 1973.PubMedCrossRefGoogle Scholar
  8. 8.
    Kleinhofs, A., and Behki, R.: Prospects for plant genome modification by nonconventional methods. In Annual Review of Genetics, Vol. 11 (H. L. Roman, ed.), Annual Reviews, Palo Alto, Calif., pp. 79–101, 1977.Google Scholar
  9. 9.
    Kreig, D. R.: Specificity of chemical mutagenesis. In Progress in Nucleic Acid Research, Vol. 2 (J. N. Davidson and W. E. Cohn, eds.), Academic Press, New York, pp. 125–68, 1963.Google Scholar
  10. 10.
    Machemer, L., and Lorke, D.: Experiences with the dominant lethal test in female mice: effects of alkylating agents and artificial sweeteners on pre-ovulatory oocyte stages. Mutat. Res. 29: 209, 1975.PubMedCrossRefGoogle Scholar
  11. 11.
    Matter, B. E., and Grauwiler, J.: Micronuclei in mouse bone marrow cells. A simple in vivo model for the evaluation of drug induced chromosomal aberrations. Mutat. Res. 23: 239–249, 1974.PubMedCrossRefGoogle Scholar
  12. 12.
    Ris, H.: Chromosome structure. In Chemical Basis of Heredity ( W. D. McElroy and B. Glass, eds.), The John Hopkins Press, Baltimore, 1957.Google Scholar
  13. 13.
    San, R. H. C., and Stich, H. F.: DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens. Int. J. Cancer 16: 284–291, 1975.PubMedCrossRefGoogle Scholar
  14. 14.
    Schmid, W.: Chemical mutagen testing on in vivo somatic mammalian cells. Agents Actions 3: 77–85, 1973.PubMedCrossRefGoogle Scholar
  15. 15.
    Setlow, R. B.: Repair deficient human disorders and cancer. Nature (London) 271: 713–717, 1978.CrossRefGoogle Scholar
  16. 16.
    Slater, E. E., Anderson, M. D., and Rosenkranz, H. S.: Rapid detection of mutagens and carcinogens. Cancer Res. 31: 970–73, 1971.PubMedGoogle Scholar
  17. 17.
    Starlinger, P.: DNA rearrangements in procaryotes. In Annual Review of Genetics, Vol. 11 (H. L. Roman, ed.), Annual Reviews, Palo Alto, Calif., pp. 103–26, 1977.Google Scholar
  18. 18.
    Stellwagen, R. H., and Cole, R. D.: Chromosomal proteins. Ann. Rev. Biochem. 38: 951–90, 1969.PubMedCrossRefGoogle Scholar
  19. 19.
    Strickberger, M. W.: Genetics. Macmillan, New York, 1968.Google Scholar
  20. 20.
    Taylor, J. H.: Sister chromatid exchanges in tritium-labeled chromosomes. Genetics 43: 515–529, 1958.PubMedGoogle Scholar
  21. 21.
    Vogel, E., and Sobels, F. H.: The function of Drosophila in genetic toxicology testing. In Chemical Mutagens: Principles and Methods for Their Detection, Vol. 4 (A. Hollaender, ed.), Plenum Press, New York, Chapter 38, pp. 93–142, 1976.Google Scholar
  22. 22.
    Williams, G. M.: The detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 37: 1845–1851, 1977.PubMedGoogle Scholar
  23. 23.
    Wolff, S., and Perry, P.: Differential Giemsa staining of sister chromatids and the study of sister chromatid exchange without autoradiography. Chromosoma 48: 341–353, 1974.PubMedCrossRefGoogle Scholar
  24. 24.
    Yanofsky, C., Drapeau, G. R., Guest, J. R., and Carlton, B. C.: The complete amino acid sequence of the tryptophan synthetase A protein (a subunit) and its colinear relationship with the genetic map of the A gene. In Papers on Genetics: A Book of Readings (Louis Levine, ed.), C. V. Mosby, St. Louis, pp. 335–37, 1971.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • David J. Brusick
    • 1
  1. 1.Litton BioneticsKensingtonUSA

Personalised recommendations