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. 1987 Dec;76:29–32. doi: 10.1289/ehp.877629

Nearest neighbor affects G:C to A:T transitions induced by alkylating agents.

B W Glickman 1, M J Horsfall 1, A J Gordon 1, P A Burns 1
PMCID: PMC1474466  PMID: 3329097

Abstract

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference was not seen following treatment with ethylmethanesulfonate. The observed preference for 5'PuG-3' site over 5'-PyG-3' sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott P. J., Saffhill R. DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O(6)-methylguanine. Biochim Biophys Acta. 1979 Mar 28;562(1):51–61. doi: 10.1016/0005-2787(79)90125-4. [DOI] [PubMed] [Google Scholar]
  2. Benzer S. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE. Proc Natl Acad Sci U S A. 1961 Mar;47(3):403–415. doi: 10.1073/pnas.47.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhanot O. S., Ray A. The in vivo mutagenic frequency and specificity of O6-methylguanine in phi X174 replicative form DNA. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7348–7352. doi: 10.1073/pnas.83.19.7348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burns P. A., Allen F. L., Glickman B. W. DNA sequence analysis of mutagenicity and site specificity of ethyl methanesulfonate in Uvr+ and UvrB- strains of Escherichia coli. Genetics. 1986 Aug;113(4):811–819. doi: 10.1093/genetics/113.4.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burns P. A., Gordon A. J., Glickman B. W. Influence of neighbouring base sequence on N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis in the lacI gene of Escherichia coli. J Mol Biol. 1987 Apr 5;194(3):385–390. doi: 10.1016/0022-2836(87)90668-1. [DOI] [PubMed] [Google Scholar]
  6. Conkling M. A., Koch R. E., Drake J. W. Determination of mutation rates in bacteriophage T4 by unneighborly base pairs: genetic analysis. J Mol Biol. 1980 Nov 5;143(3):303–315. doi: 10.1016/0022-2836(80)90192-8. [DOI] [PubMed] [Google Scholar]
  7. Farabaugh P. J. Sequence of the lacI gene. Nature. 1978 Aug 24;274(5673):765–769. doi: 10.1038/274765a0. [DOI] [PubMed] [Google Scholar]
  8. Fix D. F., Glickman B. W. Differential enhancement of spontaneous transition mutations in the lacI gene of an Ung- strain of Escherichia coli. Mutat Res. 1986 Oct;175(2):41–45. doi: 10.1016/0165-7992(86)90123-5. [DOI] [PubMed] [Google Scholar]
  9. Glickman B. W., Ripley L. S. Structural intermediates of deletion mutagenesis: a role for palindromic DNA. Proc Natl Acad Sci U S A. 1984 Jan;81(2):512–516. doi: 10.1073/pnas.81.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goth R., Rajewsky M. F. Persistence of O6-ethylguanine in rat-brain DNA: correlation with nervous system-specific carcinogenesis by ethylnitrosourea. Proc Natl Acad Sci U S A. 1974 Mar;71(3):639–643. doi: 10.1073/pnas.71.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Loechler E. L., Green C. L., Essigmann J. M. In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6271–6275. doi: 10.1073/pnas.81.20.6271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mattes W. B., Hartley J. A., Kohn K. W. DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards. Nucleic Acids Res. 1986 Apr 11;14(7):2971–2987. doi: 10.1093/nar/14.7.2971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mehta J. R., Ludlum D. B. Synthesis and properties of O6-methyldeoxyguanylic acid and its copolymers with deoxycytidylic acid. Biochim Biophys Acta. 1978 Dec 21;521(2):770–778. doi: 10.1016/0005-2787(78)90316-7. [DOI] [PubMed] [Google Scholar]
  14. Pegg A. E. Methylation of the O6 position of guanine in DNA is the most likely initiating event in carcinogenesis by methylating agents. Cancer Invest. 1984;2(3):223–231. doi: 10.3109/07357908409104376. [DOI] [PubMed] [Google Scholar]
  15. Preston B. D., Singer B., Loeb L. A. Mutagenic potential of O4-methylthymine in vivo determined by an enzymatic approach to site-specific mutagenesis. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8501–8505. doi: 10.1073/pnas.83.22.8501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pullman A., Pullman B. Molecular electrostatic potential of the nucleic acids. Q Rev Biophys. 1981 Aug;14(3):289–380. doi: 10.1017/s0033583500002341. [DOI] [PubMed] [Google Scholar]
  17. Richardson K. K., Richardson F. C., Crosby R. M., Swenberg J. A., Skopek T. R. DNA base changes and alkylation following in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea or N-ethyl-N-nitrosourea. Proc Natl Acad Sci U S A. 1987 Jan;84(2):344–348. doi: 10.1073/pnas.84.2.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schaaper R. M., Danforth B. N., Glickman B. W. Rapid repeated cloning of mutant lac repressor genes. Gene. 1985;39(2-3):181–189. doi: 10.1016/0378-1119(85)90312-9. [DOI] [PubMed] [Google Scholar]
  19. Schendel P. F., Robins P. E. Repair of O6-methylguanine in adapted Escherichia coli. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6017–6020. doi: 10.1073/pnas.75.12.6017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Swenberg J. A., Dyroff M. C., Bedell M. A., Popp J. A., Huh N., Kirstein U., Rajewsky M. F. O4-ethyldeoxythymidine, but not O6-ethyldeoxyguanosine, accumulates in hepatocyte DNA of rats exposed continuously to diethylnitrosamine. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1692–1695. doi: 10.1073/pnas.81.6.1692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Topal M. D., Eadie J. S., Conrad M. O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine. J Biol Chem. 1986 Jul 25;261(21):9879–9885. [PubMed] [Google Scholar]
  22. Zarbl H., Sukumar S., Arthur A. V., Martin-Zanca D., Barbacid M. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. 1985 May 30-Jun 5Nature. 315(6018):382–385. doi: 10.1038/315382a0. [DOI] [PubMed] [Google Scholar]

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