Advertisement

Mutagenic Consequences of the Alteration of DNA by Chemicals and Radiation

  • Bernard Strauss
  • Edith Turkington
  • Jhy Wang
  • Daphna Sagher
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)

Abstract

The induction of mutations in vivo is a process that involves the interaction of exogenous agents, the Biologically Reactive Intermediates (BRIs), with particular nucleotides in the DNA. The finding of “hot spots” (see Hsia et al., 1989) and of “mutator” strains of organisms (Modrich, 1987) indicates that superimposed on the primary interaction of BRIs and nucleotides is an effect of DNA sequence (Burns et al., 1987) and of the proteins involved in replication and in the monitoring of the DNA. Many of the primary interactions of BRIs with DNA result in alterations which block DNA synthesis, at least in vitro. It appears to be a truism that mutation, at least point mutation as a result of damage induced by an agent which inhibits DNA synthesis, requires that the DNA synthetic machinery should bypass the damage by some mechanism. An understanding of the phenomena of mutation therefore requires knowledge of the relationships between the altered DNA bases, the arrest of DNA synthesis, and the location of the damage within the DNA sequence. For example, one might assume that the sites most subject to modification by BRIs are those at which mutation occurs most readily. In fact, it appears that this simplest of hypotheses is not inevitably so, and that other factors may intervene (Brash et al., 1987).

Keywords

Transfection Efficiency Acetyl Aminofluorene Termination Band Spontaneous Termination Pause Site 
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. Brash, D., Seetharam, S., Kraemer, K., Seidman, M. and Bredberg, A. (1987). Photoproduct frequency is not the major determinant of UV base substitution hot spots or cold spots in human cells. Proc. Natl. Acad. Sci. USA. 84, 3782–3786.CrossRefGoogle Scholar
  2. Burns, P., Gordon, A. and Glickman, B. (1987). Influence of neighbouring base seqeunce on N-methyl-N’-nitro-N-nitrosoguanidine mutagenesis in the lacI gene of Escherichia coli. J. Mol. Biol. 194, 385–390.CrossRefPubMedGoogle Scholar
  3. Hsia, H., Lebkowski, J., Leong, P., Calos, M. and Miller, J. (1989). Comparison of ultraviolet-induced mutagenesis of the lacI gene in Escherichia colt and in human 293 cells. J. Mol. Biol. 205, 103–113.CrossRefPubMedGoogle Scholar
  4. Kriek, E., Miller, J., Juhl, U. and Miller, E.C. (1967). 8-(N-2-Fluorenylacetamido) guanosine, an arylamidation reaction product of guanosine and the carcinogen N-acetoxy-N-2-fluorenylacetamide in neutral solution. Carcinogenesis 6, 177–182.Google Scholar
  5. Kunkel, T. and Alexander, P. (1986). The base substitution fidelity of eucaryotic DNA polymerases. Mispairing frequencies, site-preferences, insertion preferences and base substitution by dislocation. J. Biol. Chem. 261, 160–166.PubMedGoogle Scholar
  6. Lutgerink, J., Retel, J., Westra, J., Welling, M., Loman, H. and Kriek, E. (1985). By-pass of the major aminofluorene-DNA adduct during in vivo replication of single-and double-stranded LX174 DNA treated with N-hydroxy-2-aminofluorene. Carcinogenesis 6, 1501–1506.CrossRefPubMedGoogle Scholar
  7. Modrich, P. (1987). DNA mismatch correction. Ann. Rev. Biochem. 56, 435–466.CrossRefPubMedGoogle Scholar
  8. Moore, P., Rabkin, S. and Strauss, B.S. (1980). Termination of in vitro DNA synthesis at AAF adducts in the DNA. Nuc/eic Acids Res. 8, 4473–4484.CrossRefGoogle Scholar
  9. Moore, P., Rabkin, S., Osborn, A., King, C. and Strauss, B.S. (1982). Effect of acetylated and deacetylated 2-aminofluorene adducts on in vitro DNA synthesis. Proc. Natl. Acad. Sci. USA. 79, 7166–7170.CrossRefPubMedGoogle Scholar
  10. Norman, D., Abuaf, P., Hingerty, B., Live, D., Grunberger, D., Broyde, S. and Patel, D. (1989). NMR and computational characterization of the N-(Deoxyguanosin-8-y1) aminofluorene adduct RAF)G] opposite adenosine in DNA: (AF)G[synY A[anti] pair formation and its pH dependence. Biochemistry 28, 7462–7476.CrossRefPubMedGoogle Scholar
  11. Sahm, J., Turkington, E., LaPointe, D. and Strauss, B. (1989). Mutation induced in vitro on a C-8 Guanine Aminofluorene containing template by a modified T7 DNA polymerase. Biochemistry 28, 2836–2843.CrossRefPubMedGoogle Scholar
  12. Tang, M., and Lieberman, M. (1983). Quantification of adducts formed in DNA treated with N-acetoxy-2-acetylaminofluorene or N-hydroxy-2-aminofluorene: comparison of trifluoroacetic acid and enzymatic degradation. Carcinogenesis 4, 1001–1006.CrossRefPubMedGoogle Scholar
  13. van Touw, J., Verberne, J., Retel, J. and Loman, H. (1985). Radiation-induced strand breaks in LX174 replicative form DNA: an improved experimental and theoretical approach. Int. J. Radiat. Biol. 48, 567–578.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Bernard Strauss
    • 1
  • Edith Turkington
    • 1
  • Jhy Wang
    • 1
  • Daphna Sagher
    • 1
  1. 1.Department of Molecular Genetics and Cell BiologyThe University of ChicagoChicagoUSA

Personalised recommendations