Abstract

The effects of pre/postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on various immunological, bone marrow and host susceptibility assays were examined in B6C3F1 hybrid mice. Exposure was accomplished by maternal dosing on Day 14 of gestation and again on Days 1, 7, and 14 following birth, employing dosages of 0, 1.0, 5.0 or 15.0 micrograms/kg body weight. The 15.0 micrograms/kg dosage was lethal to 70% of the offspring with the remainder of that dosage group revealing overt toxicity. Bone marrow toxicity occurred in both the 15.0 and 5.0 micrograms/kg dosage groups as evidenced by bone marrow hypocellularity and depressed colony formation of macrophage-granulocyte progenitor cells and pleuripotent stem cells. Evidence was presented that depression of lymphoproliferative responses following mitogen stimulation in TCDD-immunosuppressed mice was due to a functional defect of lymphocyte activation rather than suppressor cell activity. Administration of either Listeria monocytogenes or syngeneic PYB6 tumor cells in mice exposed to relatively low levels of TCDD during pre- and postnatal development increased their susceptibility to either bacterial or tumor challenge.