Mapping of altromycin B-DNA adduct at nucleotide resolution in the human genomic DNA by ligation-mediated PCR

Mol Cells. 2000 Feb 29;10(1):71-5. doi: 10.1007/s10059-000-0071-z.

Abstract

The ligation-mediated PCR was used to map DNA alkylation sites induced by altromycin B at nucleotide resolution in genomic DNA purified from cultured human colon carcinoma. Altromycin B, one of the pluramycin group of antitumor antibiotics, is characterized as intercalator with the added ability to alkylate N7 guanine. DNA adducts formed in genomic DNA were cleaved into DNA strand breaks by hot piperidine treatment, and fragments containing ligatable breaks were then amplified in a single-sided, ligation-mediated PCR. The alkylation sites observed in exon 9 of the p53 gene revealed that the most high reactivity sites for altromycin B were found to be N7 of guanine in a 5'-AG* sequence. Determination of the DNA alkylation sites in naked radiolabeled plasmid DNA also showed that altromycin B preferred N7 of guanine in a 5'-AG* sequence. Thus, it can be concluded that the sequence selective DNA adduct formation induced by the intercalating alkylator, altromycin B, in genomic DNA is similar to that observed in naked plasmid DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Aminoglycosides*
  • Anti-Bacterial Agents / pharmacology*
  • Base Sequence
  • Binding Sites
  • DNA / chemistry
  • DNA / genetics*
  • DNA / metabolism
  • DNA Adducts / drug effects*
  • DNA Adducts / genetics
  • Humans
  • Molecular Sequence Data
  • Plasmids / chemistry
  • Plasmids / genetics
  • Plasmids / metabolism
  • Polymerase Chain Reaction / methods
  • Sequence Analysis, DNA
  • Tumor Cells, Cultured

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • DNA Adducts
  • altromycin B
  • DNA

Associated data

  • GENBANK/AF135120