A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin produces a time- and dose-dependent alteration in the murine bone marrow B-lymphocyte maturation profile.
A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin produces a time- and dose-dependent alteration in the murine bone marrow B-lymphocyte maturation profile.
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单剂量的 2,3,7,8-四氯二苯并-对-二恶英会对小鼠骨髓 B 淋巴细胞成熟谱产生时间和剂量依赖性的改变。
DOI：
10.1093/toxsci/58.1.88
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Gasiewicz,TA
中科院分区：
文献类型：
--
作者：
Thurmond,TS;Gasiewicz,TA
卤代芳烃，2，3，7，8-四氯二苯并对二恶英（TCDD），是一种普遍存在的高毒性环境污染物，对哺乳动物产生免疫毒性作用。尽管其免疫毒性已被广泛报道，但关于其对免疫系统细胞，特别是B淋巴细胞发育的影响知之甚少。本研究的目的是评估TCDD单次给药随时间推移对骨髓B细胞祖细胞和前/前B-、未成熟B-和成熟B细胞亚群的影响，并建立这些变化的剂量-反应关系。结果表明，成熟B淋巴细胞亚群的变化具有时间依赖性，在四氯二苯并对二恶英处理（30微克/千克体重[bw]）后一天显著增加，随后在第9天显著下降，到第31天恢复到接近载体水平。发育和不太成熟的亚群显着减少，在第6和第9天。最早的B细胞祖细胞亚群增加，直到第9天，然后下降到溶剂处理的水平。处理后2天的剂量反应（30、15、9、6、3和0.3微克四氯二苯并对二恶英/千克体重）结果表明，在这些剂量下，只有成熟的B亚群受到影响，低于6微克/千克体重时没有观察到影响。这些数据表明，TCDD的主要影响是对那些进入，和/或内，成熟的B淋巴细胞亚群的细胞，并在早期成熟阶段观察到的变化是对这些成熟细胞的影响的补偿反应。
The halogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a ubiquitous, highly toxic environmental contaminant shown to produce immunotoxic effects in mammals. Although its immunotoxicity has been widely reported, little is known regarding its effect upon the development of immune-system cells, especially the B lymphocyte. The present study's purpose was to assess the effect that a single-dose administration of TCDD has, over time, upon bone marrow B-cell progenitors and pro/pre-B-, immature B-, and mature B-cell subpopulations, and to establish a dose-response relationship for these changes. Results showed that the mature B-lymphocyte subpopulation varied in a time-dependent manner, with a significant increase one day following TCDD treatment (30 μg/kg body weight [bw]), followed by a significant decrease at day 9 and a return to near-vehicle levels by day 31. Developing and less mature subpopulations were significantly decreased at days 6 and 9. The earliest B cell-progenitor subpopulation increased until day 9 and then decreased to vehicle-treated levels. Dose response (30, 15, 9, 6, 3, and 0.3 μg TCDD/kg bw) results at 2 days following treatment showed that only the mature-B subpopulation was affected at these doses, and below 6 μg/kg bw no effect was observed. These data suggest that the primary effect of TCDD is on those cells entering, and/or within, the mature B-lymphocyte subpopulation, and the alteration observed in the earlier maturation stages is a compensatory response to the effect on these mature cells.