Cellular senescence is characterized by the permanent loss of cell proliferation. Little is known about oxidative DNA damage and its relationship to molecular changes during cellular senescence. Hydrogen peroxide can induce human diploid fibroblast cells to develop senescent phenotype, providing an ideal model for determining the contribution of oxidative damage and molecular events in growth cessation. I propose to examine whether oxidative DNA damage serves as a signal activating the tumor suppressor gene p53 and pRB governed cell cycle check points and to explore the synergistic or parallel mechanisms. The experiments are designed to determine cell cycle parameters, involvement of p53 and pRB, contribution of oxidative DNA damage, and gene expressions during the development of hydrogen peroxide induced senescence. The study will provide new insights into the mechanism of growth cessation and cellular aging.
