RESPONSE OF A PRIMARY HUMAN FIBROBLAST CELL-LINE TO H2O2 - SENESCENCE-LIKE GROWTH ARREST OR APOPTOSIS

Hydrogen peroxide has been shown to induce either apoptosis or feature s of senescence in different cultured cell lines. We now show that bot h processes can be induced in the same culture of primary human diploi d fibroblasts and that the outcome of apoptosis or the senescence-like phenotype is determined by the H2O2 concentrations, At 50 and 100 mu M, H2O2 predominantly induced the senescence-like state, characterized by a reduced rate of proliferation, an increased number of cells in G (0)-G(1), typically enlarged and flattened morphology, and increased C IP1 and fibronectin expression, At 300 and 400 mu M, H2O2 mainly trigg ered apoptosis. At the intermediate 200 mu M H2O2, features of both se nescence and apoptosis were observed in the same culture, Thus, the hi gher the H2O2 concentration, the higher the proportion of cells underg oing apoptosis, suggesting a key role of the level of damage in the ch oice of a cell population to enter apoptosis and/or the senescence-lik e state, Before the induction of one or the other process, cells enter ed a transient ''shock state'' characterized by a typical morphologica l change, cell cycle arrest in G(0)G(1), and the induction of CIP1 and BCL-2.