Hyperoxia-induced DNA Damage Causes Decreased DNA Methylation in Human Lung Epithelial-Like A549 Cells

Antioxid Redox Signal. 2004 Feb;6(1):129-36. doi: 10.1089/152308604771978435.

Abstract

The effect of hyperoxia on levels of DNA damage and global DNA methylation was examined in lung epithelial-like A549 cells. DNA damage was assessed by the single-cell gel electrophoresis (comet assay) and DNA methylation status by the cytosine extension assays. Cells exposed to ionizing radiation (0, 1, 2, 4, or 8 Gy) showed increasing rates of percentage of DNA in the tail and tail length with increasing radiation dose. When cells were exposed to room air (normoxia) for 1 day and 95% O2 (hyperoxia) for 1, 2, 3, 4, and 5 days, data indicated that hyperoxia caused time-dependent increases in levels of (a) single strand breaks, (b) double strand breaks, and (c) 8-oxoguanine. Decreased DNA methylation also was observed at day 5 of hyperoxic exposure, suggesting that hyperoxia-induced DNA damage can influence patterns of DNA methylation in a lung-derived cell line.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Comet Assay / methods
  • DNA / analysis
  • DNA / drug effects
  • DNA / radiation effects
  • DNA Damage*
  • DNA Methylation / drug effects*
  • DNA Methylation / radiation effects
  • DNA Repair
  • DNA, Single-Stranded / drug effects
  • DNA, Single-Stranded / radiation effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Humans
  • Hyperoxia / physiopathology*
  • Lung Neoplasms
  • Oxygen / toxicity*
  • Time Factors

Substances

  • DNA, Single-Stranded
  • 8-hydroxyguanine
  • Guanine
  • DNA
  • Oxygen