title: 7-Methylguanine adducts in DNA are normally present at high levels and increase on aging: analysis by HPLC with electrochemical detection.
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.
authors.affiliation: Department of Biochemistry, University of California, Berkeley 94720.
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: B N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000378:metabolism; D004563:Electrochemistry; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000648:ultrastructure; D008745:Methylation; D008928:Mitochondria / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004272:DNA, Mitochondrial; D006147:Guanine; C008450:7-methylguanine; D004247:DNA