Age-related changes in oxidative DNA damage and benzo(a)pyrene diolepoxide-I (BPDE-I)-DNA adduct levels in human stomach

J Toxicol Environ Health A. 2005 Oct 8;68(19):1599-610. doi: 10.1080/15287390500182818.

Abstract

This study was conducted in order to obtain information on the association between age and oxidative DNA damage and benzo[a]pyrene diolepoxide-I (BPDE-I)-DNA adduct levels in the stomach tissues of normal subjects (n = 113). Subjects ranged from 17 to 75 yr. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were measured by high-performance liquid chromatography-electrochemical detector (HPLC-ECD). BPDE-I-DNA adduct levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) using the monoclonal antibody 8E11. Increase in 8-OHdG levels was observed in subjects from 31 to 60 yr of age. Higher levels of 8-OHdG were observed in the stomach tissues of those in the 51-60 yr old group. Although Helicobacter. Pylori-positive group subjects had higher 8-OHdG levels than those in the H. pylori-negative group, no age-related changes in 8-OHdG levels were observed in these groups. The levels of BPDE-I-DNA adduct also markedly increased with age. Higher levels of BPDE-I-DNA adduct were observed in subjects aged 61-70 yr, but this difference was not significant from other age groups. These results provide evidence that there is a progressive age-dependent accumulation of oxidative DNA damage and of BPDE-I-DNA adducts in human stomach tissues. It is possible that such damage contributes to the known increased incidence of gastric tumor with aging.

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / metabolism*
  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Benzopyrenes / metabolism*
  • Child
  • Chromatography, High Pressure Liquid
  • DNA Adducts / metabolism*
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Female
  • Gastric Mucosa / metabolism*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Stomach Neoplasms / metabolism*

Substances

  • Benzopyrenes
  • DNA Adducts
  • benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • benzo(a)pyrene diolepoxide I
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine