Nucleic Acids Research, Vol 27, Issue 11 2310-2314, Copyright © 1999 by Oxford University Press
X Tan, N Suzuki, F Johnson, AP Grollman and S Shibutani
The DNA adduct 8-amino-2'-deoxyguanosine (8-amino-dG) is found in liver DNA
of rats treated with the hepatocarcinogen 2-nitropropane. Site-
specifically modified oligodeoxynucleotides were used to explore the
mutagenic potential of 8-amino-dG in simian kidney (COS-7) cells.
Oligodeoxynucleotides (5'-TCCTCCTX1G2CCTCTC and 5'-TCCTCCTG1X2CCTCTC, X =
dG or 8-amino-dG) with the lesion positioned at codon 60 or 61 of the
non-coding strand of the human c-Ha- ras1 gene were inserted into
single-stranded phagemid vectors and transfected into COS-7 cells. The
progeny plasmid obtained was used to transform Escherichia coli DH10B.
Transformants were analyzed by oligodeoxynucleotide hybridization and DNA
sequencing to establish the mutation frequency and spectrum produced by the
modified base. The correct base, dCMP, was incorporated preferentially
opposite 8-amino-dG at X1and X2. When 8-amino-dG was at X1, targeted
GNH2-->T transversions were detected, along with smaller numbers of
GNH2-->A transitions and GNH2-->C transversions. When the adduct was
at X2, only GNH2-->T transversions were observed. The frequencies of
targeted mutation at X1and X2were 2.7 and 1.7%, respectively. Mutation
frequency and mutagenic spectrum were sequence context dependent. In
addition, non-targeted G-->T transversions, accompanied by some G-->A
transitions, were detected 5' to 8-amino-dG when the lesion was at X2. We
conclude that 8-amino-dG is a mutagenic lesion, generating G-->T and
G-->C transversions and G-->A transitions in mammalian cells.
ARTICLES
Mutagenic properties of the 8-amino-2'-deoxyguanosine DNA adduct in mammalian cells
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. A. VanderVeen, M. F. Hashim, Y. Shyr, and L. J. Marnett Induction of frameshift and base pair substitution mutations by the major DNA adduct of the endogenous carcinogen malondialdehyde PNAS, November 25, 2003; 100(24): 14247 - 14252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Venkatarangan, A. Sivaprasad, F. Johnson, and A. K. Basu Site-specifically located 8-amino-2'-deoxyguanosine: thermodynamic stability and mutagenic properties in Escherichia coli Nucleic Acids Res., April 1, 2001; 29(7): 1458 - 1463. [Abstract] [Full Text] [PDF]
|
|