Effects of reactive oxygen species on proliferation of Chinese hamster lung fibroblast (V79) cells

Reactive oxygen species (ROS) have emerged as important signaling molecules in the regulation of various cellular processes. In our study, we investig ated the effect of a wide range of ROS on Chinese hamster lung fibroblast ( V79) cell proliferation. Treatment with H2O2 (100 muM), superoxide anion (g enerated by 1 mM xanthine and 1 mU/ml xanthine oxidase), menadione, and phe nazine methosulfate increased the cell proliferation by approximately 50%. Moreover, a similar result was observed after partial inhibition of superox ide dismutase (SOD) and glutathione peroxidase. This upregulation of cell p roliferation was suppressed by pretreatment with hydroxyl radical scavenger s and iron chelating agents. In addition to ROS, treatment with exogenous c atalase and SOD mimic (MnTMPyP) suppressed the normal cell proliferation, S hort-term exposure of the cells to 100 muM H2O2 was sufficient to induce pr oliferation, which indicated that activation of the signaling pathway is im portant as an early event. Accordingly, we assessed the ability of H2O2 to activate mitogen-activated protein kinases (MAPK). Jun-N-terminal kinase (J NK) and p38 MAPK were both rapidly and transiently activated by 100 muM H2O 2, with maximal activation 30 min after treatment. However, the activity of extracellular signal-regulated kinase (ERK) was not changed. Pretreatment with SB203580 and SB202190, specific inhibitors of p38 MAPK, reduced the ce ll proliferation induced by H2O2. The activation of both JNK and p38 MAPK w as also suppressed by pretreatment with hydroxyl radical scavenger and iron chelating agents, Our results suggest that the trace metal-driven Fenton r eaction is a central mechanism that underlies cell proliferation and MAPK a ctivation. (C) 2001 Elsevier Science Inc.