Hemopoietic progenitor cells ave sensitive targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J mice
Hemopoietic progenitor cells ave sensitive targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J mice
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DOI：
10.1093/toxsci/54.2.374
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发表时间：
2000-04-01
影响因子：
3.8
通讯作者：
Gasiewicz, TA
中科院分区：
文献类型：
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作者：
Murante, FG;Gasiewicz, TA
用四氯二苯并对二恶英（TCDD）处理C57 BL/6 J螨成虫，可显著改变其骨髓造血细胞的潜能，降低T淋巴细胞的重建活性。后者被假设在TCDD诱导的胸腺萎缩中发挥作用。为了研究导致原胸腺细胞容量降低的细胞靶点，通过检查Sca-1和c-Kit水平来评估TCDC处理的C57 BL/6 J小鼠的骨髓细胞在谱系阴性（lin（-））隔室中的造血变化。用30 μ g/kg TCDD处理C57 BL/6 J小鼠，观察24小时至31天后Lin（-）造血细胞的表型改变。在TCDD处理后2天，还评估了lin（-）细胞对0.3至30 μ g/kg TCDD剂量的反应。数据显示，在给药后24 h至31天内，相对于对照组，骨髓lin（-）Sca-1（+）c-Kit（+）细胞数量增加，以及在第2天检查时，该群体的剂量依赖性增加。Lin（-）Sca-1（+）c-Kit（+）细胞的增加更短暂，也依赖于TCDD剂量。这些数据表明，造血干细胞的增殖和/或分化过程受到TCDD的影响，这些影响导致骨髓产生pro-T淋巴细胞的能力降低。
Treatment of adult C57BL/6J mite with tetrachlorodibenzo-p-dioxin (TCDD) elicits altered bone marrow hemopoietic cellular potentials and markedly reduced T-lymphoid-reconstituting activity. The latter has been hypothesized to play a role in TCDD-induced thymic atrophy. To investigate cellular targets responsible for reduced prothymocyte capacity, bone marrow cells from TCDD-treated C57BL/6J mice were assessed for hemopoietic alterations within the lineage-negative (lin(-)) compartment by the examination of Sca-1 and c-Kit levels. Lin(-) hemopoietic cells from C57BL/6J mice, treated dth 30 mu g/kg of TCDD, were assessed for phenotypic alterations following 24 h through 31 days. The responses of lin(-) cells to TCDD doses ranging from 0.3 to 30 mu g/kg were also assessed at 2 days following TCDD treatment. The data reveal increases in the number of bone marrow lin(-) Sca-1(+) c-Kit(+) cells, relative to control, over 24 h through 31 days following treatment, as well as dose-dependent increases in this population when examined at 2 days. Increases in Lin(-) Sca-1(+) c-Kit(+) cells occurred on a more transient basis and were also dependent upon TCDD dose. These data suggest that proliferation and/or differentiation processes of hemopoietic stem cells are affected by TCDD and that these effects contribute to a reduced capacity of bone marrow to generate pro-T lymphocytes.