Feasibility of 8-OHdG formation and hOGG1 induction in PBMCs for assessing oxidative DNA damage in the lung of COPD patients

Respirology. 2014 Nov;19(8):1183-90. doi: 10.1111/resp.12378. Epub 2014 Aug 25.

Abstract

Background and objective: Oxidative stress has long been recognized to play a role in chronic obstructive pulmonary disease (COPD); however, approaches for assessing oxidative stress are lacking. The objective of this study was to address the feasibility of measuring 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-OHdG) formation and human 8-oxoguanine DNA glycosylase (hOGG1) induction in peripheral blood mononuclear cell (PBMC) to assess oxidative deoxyribonucleic acid (DNA) damage in the lung of smoking COPD patients.

Methods: PBMC were obtained from 412 participants including 129 smokers with COPD, 143 healthy smokers and 140 healthy non-smokers. Lung tissue specimens and PBMC were obtained from smoker COPD (n = 12), healthy smokers (n = 12) and healthy non-smokers (n = 10). 8-OHdG and hOGG1 were detected, and correlation analysis was conducted for assessing the feasibility.

Results: Oxidative DNA damage (8-OHdG formation) along with impaired induction of hOGG1 expression in the lung was a prominent feature for smokers COPD patients. PBMC originated from smokers COPD patients also displayed similar features to that of lung tissues. Correlation analysis suggests that PBMC could be used as a surrogate for oxidative DNA damage in lung of smokers COPD patients. Indeed, 8-OHdG levels in PBMC DNA were negatively correlated with lung function, while hOGG1 induction in PBMC was associated with improved lung function in smokers COPD patients.

Conclusions: COPD patients manifest oxidative DNA damage of 8-OHdG along with impaired hOGG1 expression in the lung, whereas 8-OHdG formation and hOGG1 induction in PBMC could be a biomarker of oxidative DNA damage in the lung.

Keywords: 8-dihydro-2′-deoxyguanosine; 8-oxo-7; chronic obstructive pulmonary disease; human 8-oxoguanine DNA glycosylase; lung tissue; peripheral blood mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Biomarkers / metabolism
  • DNA Damage
  • DNA Glycosylases* / genetics
  • DNA Glycosylases* / metabolism
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / genetics
  • Deoxyguanosine / metabolism
  • Female
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Lung / pathology
  • Male
  • Middle Aged
  • Oxidative Stress / genetics*
  • Pulmonary Disease, Chronic Obstructive* / blood
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / etiology
  • Respiratory Function Tests
  • Smoking* / adverse effects
  • Smoking* / metabolism
  • Statistics as Topic

Substances

  • Biomarkers
  • 8-hydroxyguanine
  • Guanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • Deoxyguanosine