In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families

Carcinogenesis. 1995 Apr;16(4):735-41. doi: 10.1093/carcin/16.4.735.


The present study was aimed at verifying the occurrence, if any, of in vivo oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood leucocytes from FA homozygotes and their relatives and compared with a group of paediatric and adult healthy subjects. The population studied consisted of: (i) 15 FA homozygotes; (ii) 24 FA heterozygotes; (iii) 11 siblings. The 8-OHdG level in FA homozygotes was significantly higher with respect to age-matched controls, with a mean level of 33.3 +/- 6.8 (mean +/- SE) and 3.9 +/- 0.26 8-OHdG/10(5) dG respectively. The FA parents (heterozygotes) also displayed higher 8-OHdG levels relative to controls. The release of hydroxyl (.OH) and .OH-like radicals from leucocytes was determined by luminol-dependent chemiluminescence (LDCL) in a subgroup of FA homo- and heterozygotes, showing a very large in vivo formation of non-superoxide radicals. Chromosomal instability was also measured in the FA population. When relating either 8-OHdG or LDCL levels to spontaneous or diepoxybutane-induced chromosomal instability (S-CI and DEB-CI respectively), a significant correlation was observed between the 8-OHdG, LDCL and S-CI data. Within families a positive association was found between 8-OHdG levels in homozygotes and their related heterozygotes, suggesting segregation of the genetic defect(s) underlying the abnormal oxidative metabolism. The present study provides evidence for an in vivo pro-oxidant state in FA, in terms of excess formation of .OH and .OH-like radicals, and of DNA hydroxyl adducts. This finding appears to be shared by homozygotes and, to a lesser extent, by heterozygotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Chromosomes, Human
  • DNA / blood*
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / analysis
  • Deoxyguanosine / blood
  • Epoxy Compounds
  • Fanconi Anemia / blood*
  • Fanconi Anemia / genetics*
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Leukocytes / metabolism
  • Luminescent Measurements
  • Luminol
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*
  • Respiratory Burst / physiology


  • Epoxy Compounds
  • Reactive Oxygen Species
  • Luminol
  • diepoxybutane
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine