Mass spectrometric sequencing of site-specific carcinogen-modified oligodeoxyribonucleotides containing bulky benzo[a]pyrene diol epoxide-deoxyguanosyl adducts

Anal Biochem. 1998 Nov 15;264(2):222-9. doi: 10.1006/abio.1998.2835.

Abstract

Site-specific carcinogen-modified oligonucleotides are often used in site-directed mutagenesis and other biological and biochemical studies of structure-function relationships. Postsynthetic analysis and confirmation of the sites of carcinogen binding in such oligonucleotides is an important step in the characterization of these site-specific carcinogen-DNA adducts. It is shown here that negative ion mode electrospray tandem mass spectrometry methods and collision-induced dissociation offer a rapid and convenient approach for the sequencing of products derived from the reaction of the carcinogenic and mutagenic metabolite of benzo[a]pyrene, the diol epoxide r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), with the 11-mer oligonucleotide d(CATGCGGCCTAC). The site of reaction of anti-BPDE with either one of the three dG residues in this oligonucleotide can be accurately established by comparing the mass/charge ratios of the observed collision-induced dissociation fragments with calculated values.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / analysis*
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / chemical synthesis
  • Anions
  • Chromatography, High Pressure Liquid
  • DNA Adducts / analysis*
  • DNA Adducts / chemical synthesis
  • Mass Spectrometry / methods*
  • Mutagenesis, Site-Directed*
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / genetics*
  • Radioactive Tracers
  • Sequence Analysis, DNA / methods*

Substances

  • Anions
  • DNA Adducts
  • Oligodeoxyribonucleotides
  • Radioactive Tracers
  • benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide