title: The suppression of radiation-induced NF-kappaB activity by dexamethasone correlates with increased cell death in vivo.
abstract: In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory kappaBalpha (IkappaBalpha) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and gamma-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents in bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases IkappaBalpha expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-kappaB in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing IkappaBalpha expression in hematopoietic organs such as spleen and bone marrow.
authors.affiliation: Division of Radiation Effect Research, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Seoul 132-703, Republic of Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D003907:Dexamethasone