Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1

Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O-2( -))-generating NADPH oxidase of phagocytes, causes increased O-2(-) generat ion, increased mitotic rate, cell transformation, and tumorigenicity when e xpressed in NIH 3T3 fibroblasts. This study explores the role of reactive o xygen species (ROS) in regulating cell growth and transformation by Nox1. H 2O2 concentration increased approximate to 10-fold in Nox1-expressing cells , compared with <2-fold increase in O-2(-). When human catalase was express ed in Nox1-expressing cells. H2O2 concentration decreased, and the cells re verted to a normal appearance, the growth rate normalized, and cells no lon ger produced tumors in athymic mice. A large number of genes, including man y related to cell cycle, growth, and cancer (but unrelated to oxidative str ess), were expressed in Nox1-expressing cells, and more than 60% of these r eturned to normal levels on coexpression of catalase. Thus, H2O2 in low con centrations functions as an intracellular signal that triggers a genetic pr ogram related to cell growth.