Luster M I, Boorman G A, Dean J H, Harris M W, Luebke R W, Padarathsingh M L, Moore J A
Int J Immunopharmacol. 1980;2(4):301-10. doi: 10.1016/0192-0561(80)90030-2.
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.
在B6C3F1杂交小鼠中,研究了产前/产后暴露于2,3,7,8-四氯二苯并对二恶英(TCDD)对各种免疫学、骨髓和宿主易感性检测的影响。暴露通过在妊娠第14天对母体给药,并在出生后的第1、7和14天再次给药来实现,采用的剂量为0、1.0、5.0或15.0微克/千克体重。15.0微克/千克的剂量对70%的后代是致命的,该剂量组的其余部分显示出明显的毒性。15.0和5.0微克/千克剂量组均出现骨髓毒性,表现为骨髓细胞减少以及巨噬细胞-粒细胞祖细胞和多能干细胞集落形成受抑制。有证据表明,TCDD免疫抑制小鼠在有丝分裂原刺激后淋巴细胞增殖反应受到抑制是由于淋巴细胞激活的功能缺陷,而非抑制细胞活性。在产前和产后发育期间暴露于相对低水平TCDD的小鼠中,接种单核细胞增生李斯特菌或同基因PYB6肿瘤细胞会增加它们对细菌或肿瘤攻击的易感性。