SUBACUTE EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN GERIATRIC MICE: EFFECTS IN THYMIC, SPLENIC, AND BONE MARROW HEMATOPOIETIC CELLS

Abstract

Exposure of geriatric m ice (21- 1 m o) to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produced alterations in thymus, spleen, and bone m arrow hematopoietic cell populations. Female C57BL/ 6 mice were dosed (via intraperitoneal injection) with 0, 5.0, or 10.0 ug/ kg TCDD in corn oil for 5 consecutive days. Evaluation of imm une endpoints took place on the second day following cessation of dosing. A limited but significant reduction in bone marrow cellularity was produced by exposure to TCDD at 10.0 ug/ kg, in the presence of unaltered percentages of cells expressing CD45, CD45R, and Mac-1 antigens. A lim ited increase in splenic cellularity was also present at the higher dose level of TCDD, where trends toward reduced percent++ ages of CD45R B cells and Thy 1.2 T cells were observed but did not reach significance. Pronounced, dose-dependent thymic hypocellularity was evident at both levels of chemical exposure in the aged m ice, and was accom panied by+ + decreased percentages of CD4 CD8 (double positive, DP) cells and concomitant--- + increased percentages of CD4 CD8 (double negative, DN) and CD4 CD8 (single positive, SP) cells. The total numbers of thymocytes in all four phenotypes defined by CD4 and CD8 antigens decreased significantly in treated animals, an apparent reflection of the chem ical-induced hypocellularity. These results indicate that, sim ilar to perinatal and young adult m odels, the geriatric murine thym us may be a highly sensitive target of TCDD exposure.