Translesion synthesis past the C8- and N2-deoxyguanosine adducts of the dietary mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline in the NarI recognition sequence by prokaryotic DNA polymerases

Chem Res Toxicol. 2006 Nov;19(11):1506-17. doi: 10.1021/tx0601455.


2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is found in cooked meats and forms DNA adducts at the C8- and N2-positions of dGuo after appropriate activation. IQ is a potent inducer of frameshift mutations in bacteria and is carcinogenic in laboratory animals. We have incorporated both IQ-adducts into the G1- and G3-positions of the NarI recognition sequence (5'-G1G2CG3CC-3'), which is a hotspot for arylamine modification. The in vitro replication of the oligonucleotides was examined with Escherichia coli pol I Klenow fragment exo-, E. coli pol II exo-, and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), and the extension products were sequenced by tandem mass spectrometry. Replication of the C8-adduct at the G3-position resulted in two-base deletions with all three polymerases, whereas error-free bypass and extension was observed at the G1-position. The N2-adduct was bypassed and extended by all three polymerases when positioned at the G1-position, and the error-free product was observed. The N2-adduct at the G3-position was more blocking and was bypassed and extended only by Dpo4 to produce an error-free product. These results indicate that the replication of the IQ-adducts of dGuo is strongly influenced by the local sequence and the regioisomer of the adduct. These results also suggest a possible role for pol II and IV in the error-prone bypass of the C8-IQ-adduct leading to frameshift mutations in reiterated sequences, whereas noniterated sequences result in error-free bypass.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Cooking
  • DNA Adducts / chemistry*
  • DNA Replication
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / genetics
  • Deoxyguanosine / chemistry*
  • Deoxyribonucleases, Type II Site-Specific / chemistry*
  • Gene Deletion
  • Hot Temperature
  • Molecular Structure
  • Mutagens / chemistry
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry*
  • Oligonucleotides / genetics
  • Prokaryotic Cells / enzymology
  • Quinolines / chemistry*


  • DNA Adducts
  • Mutagens
  • Oligonucleotides
  • Quinolines
  • 2-amino-3-methylimidazo(4,5-f)quinoline
  • DNA-Directed DNA Polymerase
  • Deoxyribonucleases, Type II Site-Specific
  • GGCGCC-specific type II deoxyribonucleases
  • Deoxyguanosine