Carcinogenesis, Vol 18, 1561-1567, Copyright © 1997 by Oxford University Press
B Sedgwick
Mutants of Escherichia coli and Saccharomyces cerevisiae that lack O6-
alkylguanine-DNA alkyltransferase activities have increased spontaneous
mutation rates, indicating the presence of a cellular metabolite that can
alkylate DNA. Bacterially catalysed nitrosation has been implicated
previously in producing the endogenous alkylating agent(s). Here,
nitrosated polyamines and azaserine, a model compound for nitrosated
peptides, are shown to be mutagenic to E. coli ada ogt mutants deficient in
O6-alkylguanine-DNA alkyltransferase activity. The mutagenicity of
azaserine may be explained by its ability to methylate DNA, whereas
nitrosated spermidine causes DNA damage that is susceptible to both
nucleotide excision repair and O6-alkylguanine-DNA alkyltransferase
activity, which indicates the generation of more bulky DNA adducts.
Nitrosated peptides and polyamines are therefore potential endogenous
mutagens that are harmful particularly in O6-alkylguanine- DNA
alkyltransferase deficient cells.
ARTICLES
Nitrosated peptides and polyamines as endogenous mutagens in O6- alkylguanine-DNA alkyltransferase deficient cells
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Weiss Evidence for Mutagenesis by Nitric Oxide during Nitrate Metabolism in Escherichia coli J. Bacteriol., February 1, 2006; 188(3): 829 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Margison, A. C. Povey, B. Kaina, and M. F. Santibanez Koref Variability and regulation of O6-alkylguanine-DNA alkyltransferase Carcinogenesis, April 1, 2003; 24(4): 625 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Margison, M. F. Santibanez Koref, and A. C. Povey Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine Mutagenesis, November 1, 2002; 17(6): 483 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Bobola, M. S. Berger, R. G. Ellenbogen, T. S. Roberts, J. R. Geyer, and J. R. Silber O6-Methylguanine-DNA Methyltransferase in Pediatric Primary Brain Tumors: Relation to Patient and Tumor Characteristics Clin. Cancer Res., March 1, 2001; 7(3): 613 - 619. [Abstract] [Full Text]
|
|
|
|
|
|
P. Landini and M. R. Volkert Regulatory Responses of the Adaptive Response to Alkylation Damage: a Simple Regulon with Complex Regulatory Features J. Bacteriol., December 1, 2000; 182(23): 6543 - 6549. [Full Text]
|
|
|
|
 |
|
 S. A. Smith and B. P. Engelward In vivo repair of methylation damage in Aag 3-methyladenine DNA glycosylase null mouse cells Nucleic Acids Res., September 1, 2000; 28(17): 3294 - 3300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lindahl and R. D. Wood Quality Control by DNA Repair Science, December 3, 1999; 286(5446): 1897 - 1905. [Abstract] [Full Text]
|
|
|
|
|
|
L. M. Posnick and L. D. Samson Influence of S-Adenosylmethionine Pool Size on Spontaneous Mutation, Dam Methylation, and Cell Growth of Escherichia coli J. Bacteriol., November 1, 1999; 181(21): 6756 - 6762. [Abstract] [Full Text]
|
|
|
|
|
|
M. O'Driscoll, P. Macpherson, Y.-Z. Xu, and P. Karran The cytotoxicity of DNA carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells Carcinogenesis, September 1, 1999; 20(9): 1855 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Proceedings of the British Toxicology Society Annual Congress University of Surrey, Guildford 19 - 22 April 1998 Human and Experimental Toxicology, September 1, 1998; 17(9): 469 - 534. [PDF]
|
|