Peden-Adams Margie M, Eudaly Jackie G, Heesemann Lauren M, Smythe Joshua, Miller Julie, Gilkeson Gary S, Keil Deborah E
Department of Pediatrics, Medical University of South Carolina (MUSC), Charleston, South Carolina 29412, USA.
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(3):249-71. doi: 10.1080/10934520500455289.
This study assessed the developmental immunotoxicity of trichloroethylene (TCE) in B6C3F1 mice exposed via drinking water (0, 1,400, 14,000 ppb) from gestation day 0 (GD0) to either 3 or 8 weeks of age. Lymphocyte proliferation, NK cell activity, SRBC-specific IgM production (PFC response), splenic B220+ cells, and thymic and splenic T-cell immunophenotypes were assessed at 3 and 8 weeks of age. Delayed type hypersensitivity (DTH) and autoantibodies to ds-DNA were assessed in 8-week old animals only. Proliferation and NK cell activity were not affected at either age. Decreased PFC responses were noted in male offspring at both ages and both TCE treatment levels. PFC responses in female offspring were suppressed by treatment with 14,000 ppb TCE at both ages assessed and at 1,400 ppb TCE at 8 weeks of age. Splenic numbers of B220 cells were only decreased in 3-week old pups exposed to 14,000 ppb TCE. The most pronounced alteration in T-cell subpopulations were increases in all thymic (CD4+, CD8+, CD4+/CD8+, and CD4-/CD8-) T-cell types in 8-week old animals. DTH was increased in females at both TCE levels and in males at the high dose only. These results indicate that TCE may be an effective developmental immunotoxicant and suggests that additional studies are required to determine the health risks associated with developmental exposure to TCE.
本研究评估了三氯乙烯(TCE)对从妊娠第0天(GD0)开始通过饮用水(0、1400、14000 ppb)接触到3周龄或8周龄的B6C3F1小鼠的发育免疫毒性。在3周龄和8周龄时评估淋巴细胞增殖、自然杀伤(NK)细胞活性、抗绵羊红细胞特异性IgM产生(空斑形成细胞反应)、脾脏B220+细胞以及胸腺和脾脏T细胞免疫表型。仅在8周龄动物中评估迟发型超敏反应(DTH)和抗双链DNA自身抗体。在两个年龄段,增殖和NK细胞活性均未受到影响。在两个年龄段以及两种TCE处理水平下,雄性后代的空斑形成细胞反应均降低。在评估的两个年龄段以及8周龄时1400 ppb TCE处理下,雌性后代的空斑形成细胞反应均受到抑制。仅在暴露于14000 ppb TCE的3周龄幼崽中,脾脏B220细胞数量减少。在8周龄动物中,T细胞亚群最明显的变化是所有胸腺(CD4+、CD8+、CD4+/CD8+和CD4-/CD8-)T细胞类型增加。在两种TCE水平下,雌性的DTH均增加,仅在高剂量时雄性的DTH增加。这些结果表明,TCE可能是一种有效的发育免疫毒性物质,并表明需要进行更多研究以确定与发育过程中接触TCE相关的健康风险。