5-Azacytidine-induced Apoptosis in Lymphoid and Hematopoietic Organs of Adult Mice.

Abstract

The present study deals with the effects of 5-azacytidine (5AzC) on the lymphoid and hematopoietic tissues in adult mice. Seven-week-old, male BALB/c mice were injected with 5AzC (100 mg/kg) intraperitoneally, and the thymus, spleen, and bone marrow were examined for cellular proliferative activity and apoptotic changes. In 5AzC-treated mice, the number of proliferative cell nuclear antigen (PCNA)-positive cells began to decrease at 6 hours after treatment (AT) in the thymic cortex and bone marrow, and at 12 hours AT in the splenic white pulp. The number of TUNEL-positive cells strikingly increased up to 24 hours AT in the thymic cortex, to 12 hours AT in the splenic white pulp, and to 6 hours AT in the bone marrow, and decreased thereafter in all tissues. The number of immature myeloid and erythroid cells in the bone marrow decreased after 5AzC-treatment. Electron microscopic study revealed nuclear condensation and fragmentation in pyknotic or karyorrhectic thymic lymphocytes. DNA electrophoresis of the thymus and bone marrow from 5AzC-treated mice at 12 hours AT showed a typical ladder formation. These findings indicate the apoptotic effect of 5AzC on dividing lymphoid and hematopoietic cells even in adult mice.