THE PROTOONCOGENE C-FOS MEDIATES APOPTOSIS IN MURINE T-LYMPHOCYTES INDUCED BY IONIZING-RADIATION AND DEXAMETHASONE

Expression of the immediate early response gene c-fos is induced by se veral cellular and extracellular stress factors including ionizing rad iation. We examined the role of c-fos in mediating stress-induced apop tosis of isogenic CD4(+) and CD8(+) mouse T-lymphocytes differing only in their c-fos status after treatment with ionizing radiation and the synthetic glucocorticoid dexamethasone. The amount of radiation-induc ed apoptosis was decreased (up to 37%) in the T-lymphocyte population derived from the knockout mice lacking endogenous c-fos compared to th e wildtype T-lymphocyte population. The difference in apoptosis induct ion in T-lymphocytes from wildtype and c-fos knockout mice was even mo re prominent (up to 55%) after dexamethasone treatment. Comparative ex periments were performed with T-lymphocytes hom isogenic mouse litterm ates differing only in the status of the tumor suppressor gene p53. Wh ereas p53 plays a primary role in radiation-induced apoptosis, our res ults suggest that c-fos enhances both p53-dependent radiation: and p53 -independent steroid-induced apoptosis in T-lymphocytes. (C) 1997 Acad emic Press.