Keil Deborah E, Warren D Alan, Jenny Matthew J, EuDaly Jackie G, Smythe Joshua, Peden-Adams Margie M
National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505, USA.
Toxicol Sci. 2003 Dec;76(2):347-56. doi: 10.1093/toxsci/kfg244. Epub 2003 Sep 26.
Immunological parameters, host resistance, and thyroid hormones were evaluated in F1 mice exposed in utero to jet propulsion fuel-8 (JP-8). C57BL/6 pregnant dams (mated with C3H/HeJ males) were gavaged daily on gestation days 6-15 with JP-8 in a vehicle of olive oil at 0, 1000, or 2000 mg/kg. At weaning (3 weeks of age), no significant differences were observed in body, liver, spleen, or thymus weight, splenic and thymic cellularity, splenic CD4/CD8 lymphocyte subpopulations, or T-cell proliferation. Yet, lymphocytic proliferative responses to B-cell mitogens were suppressed in the 2000 mg/kg treatment group. In addition, thymic CD4-/CD8+ cells were significantly increased. By adulthood (8 weeks of age), lymphocyte proliferative responses and the alteration in thymic CD4-/CD8+ cells had returned to normal. However, splenic weight and thymic cellularity were altered, and the IgM plaque forming cell response was suppressed by 46% and 81% in the 1000 and 2000 mg/kg treatment groups, respectively. Furthermore, a 38% decrease was detected in the total T4 serum hormone level at 2000 mg/kg. In F1 adults, no significant alterations were observed in natural killer cell activity, T-cell lymphocyte proliferation, bone marrow cellularity and proliferative responses, complete blood counts, peritoneal and splenic cellularity, liver, kidney, or thymus weight, macrophage phagocytosis or nitric oxide production, splenic CD4/CD8 lymphocyte subpopulations, or total T3 serum hormone levels. Host resistance models in treated F1 adults demonstrated that immunological responses were normal after challenge with Listeria monocytogenes, but heightened susceptibility to B16F10 tumor challenge was seen at both treatment levels. This study demonstrates that prenatal exposure to JP-8 can target the developing murine fetus and result in impaired immune function and altered T4 levels in adulthood.
对子宫内暴露于喷气推进燃料-8(JP-8)的F1代小鼠的免疫参数、宿主抵抗力和甲状腺激素进行了评估。C57BL/6怀孕母鼠(与C3H/HeJ雄鼠交配)在妊娠第6至15天每天用橄榄油载体中的JP-8进行灌胃,剂量分别为0、1000或2000毫克/千克。在断奶时(3周龄),在体重、肝脏、脾脏或胸腺重量、脾脏和胸腺细胞数量、脾脏CD4/CD8淋巴细胞亚群或T细胞增殖方面未观察到显著差异。然而,在2000毫克/千克治疗组中,对B细胞有丝分裂原的淋巴细胞增殖反应受到抑制。此外,胸腺CD4-/CD8+细胞显著增加。到成年期(8周龄)时,淋巴细胞增殖反应和胸腺CD4-/CD8+细胞的改变已恢复正常。然而,脾脏重量和胸腺细胞数量发生了改变,在1000和2000毫克/千克治疗组中,IgM空斑形成细胞反应分别被抑制了46%和81%。此外,在2000毫克/千克时,总T4血清激素水平下降了38%。在F1代成年小鼠中,自然杀伤细胞活性、T细胞淋巴细胞增殖、骨髓细胞数量和增殖反应、全血细胞计数、腹膜和脾脏细胞数量、肝脏、肾脏或胸腺重量、巨噬细胞吞噬作用或一氧化氮产生、脾脏CD4/CD8淋巴细胞亚群或总T3血清激素水平均未观察到显著改变。经处理的F1代成年小鼠的宿主抵抗力模型表明,在用单核细胞增生李斯特菌攻击后免疫反应正常,但在两个治疗水平上均观察到对B16F10肿瘤攻击的易感性增加。这项研究表明,产前暴露于JP-8可针对发育中的小鼠胎儿,导致成年期免疫功能受损和T4水平改变。