Dinstinct ROS and biochemical profiles in cells undergoing DNA damage-induced senescence and apoptosis

Cellular senescence and apoptosis are both caused by DNA damage stresses, and their severity appears to decide between the two cellular outcomes. In recent studies, it is suggested that these two states may be closely linked and be switched by certain molecular determinants such as p21WAF1 and caspase (Abdelhadi, 2003). However, it is unknown how the pathways to senescence and apoptosis are determined. In addition, although DNA damage stresses frequently accompany cellular accumulation of reactive oxygen species (ROS), how ROS are involved in the decision between the two pathways is unknown. In the present study, MCF-7 cells were induced to senescence or apoptosis by the treatment of varying doses of adriamycin. And, through a series of time course studies, ROS generation profiles and changes in the status of the proteins involved in growth regulation and apoptosis were determined. Significant levels of ROS were produced in senescing cells but not in apoptotic cells. Therefore, senescence is associated with ROS accumulation, but apoptosis is caused independently of ROS. In addition, cells in these two states exhibited quite distinct time course profiles of the proteins, p53, p21WAF1, and E2F1. (c) 2004 Elsevier Ireland Ltd. All rights reserved.