7-Methylguanine adducts in DNA are normally present at high levels and increase on aging: analysis by HPLC with electrochemical detection

Proc Natl Acad Sci U S A. 1988 Oct;85(20):7467-70. doi: 10.1073/pnas.85.20.7467.

Abstract

The 7-methylguanine adduct in the DNA of rat liver is determined as an indicator of exposure to exogenous and endogenous methylating agents. A method for the analysis of 7-methylguanine adducts has been developed by combining the selectivity of separation of reversed-phase HPLC with the specificity and high sensitivity of electrochemical detection. The sensitivity of the method is about 10,000-fold that of optical methods and is sufficient to determine the endogenous background of DNA methylation. DNA from the liver of normal young rats (6 months old) contains 7-methylguanine at a level of 1 residue per 31,000 bases in mitochondrial DNA and 1 residue per 105,000 bases in nuclear DNA. These levels increase about 2.5-fold in old rats (24 months old). We attribute this strikingly high level of adducts to endogenous methylation, which could contribute to aging and cancer.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cell Nucleus / analysis
  • Chromatography, High Pressure Liquid
  • DNA / analysis*
  • DNA / metabolism
  • DNA, Mitochondrial / analysis*
  • DNA, Mitochondrial / metabolism
  • Electrochemistry
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / analysis
  • Liver / analysis
  • Liver / ultrastructure
  • Methylation
  • Mitochondria / analysis
  • Rats
  • Rats, Inbred Strains

Substances

  • DNA, Mitochondrial
  • Guanine
  • 7-methylguanine
  • DNA