Growth arrest in G1 protects against oxygen-induced DNA damage and cell death

J Cell Physiol. 2002 Oct;193(1):26-36. doi: 10.1002/jcp.10146.


Although oxygen is required for normal aerobic respiration, hyperoxia (95% O(2)/5% CO(2)) damages DNA, inhibits proliferation in G1, S and G2 phases of the cell cycle, and induces necrosis. The current study examines whether growth arrest in G1 protects pulmonary epithelial cells from oxidative DNA damage and cell death. Mv1Lu pulmonary adenocarcinoma cells were chosen for studies because hyperoxia inhibits their proliferation in S and G2 phase, while they can be induced to arrest in G1 by altering culture conditions. Hyperoxia inhibited proliferation, increased intracellular redox, and rapidly reduced clonogenic survival. In contrast, Mv1Lu cells treated with transforming growth factor (TGF)-beta1, deprived of serum or grown to confluency, arrested and remained predominantly in G1 even during exposure. Growth arrest in G1 significantly enhanced clonogenic survival by 10-50-fold. Enhanced survival was not due to reduction in the intracellular redox-state of the cells, but instead was associated with reduced DNA strand breaks and p53 expression. Our findings suggest that the protective effects of G1 is mediated not simply by a reduction in intracellular ROS, but rather through an enhanced ability to limit or rapidly recognize and repair damaged DNA.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Animals
  • Blotting, Western
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Comet Assay
  • Culture Media, Serum-Free / pharmacology
  • DNA Damage*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Flow Cytometry
  • G1 Phase*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Mink
  • Oxidation-Reduction
  • Oxygen / toxicity*
  • Time Factors
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • Culture Media, Serum-Free
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • Oxygen