Kim S, Stair E L, Lochmiller R L, Lish J W, Qualls C W
Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, USA.
J Toxicol Environ Health A. 2001 Jan 26;62(2):83-96. doi: 10.1080/009841001455508.
Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.
骨髓对毒物极其敏感，在实验室啮齿动物中，骨髓祖细胞的体外培养已被证明是骨髓损伤的敏感指标。研究了骨髓祖细胞检测法在野生啮齿动物模型（棉鼠，棉鼠属）中检测骨髓毒性的能力，该模型栖息于美国南部许多受污染的生态系统中。测定祖细胞对重组鼠粒细胞巨噬细胞集落刺激因子（GM-CSF）和棉鼠肺条件培养基（LCM）的反应性，以优化棉鼠的培养条件。在5天的时间内，用环磷酰胺（8或80mg/kg）或地塞米松（500μg/kg）处理棉鼠，诱导其产生骨髓毒性。高剂量环磷酰胺的给药导致粒细胞巨噬细胞祖细胞（CFU-GM）的集落形成几乎完全受到抑制。在高剂量环磷酰胺处理的棉鼠中，还观察到骨髓和脾脏有明显的组织学变化。虽然组织学病变不明显，但与对照组相比，低剂量环磷酰胺和地塞米松处理的棉鼠骨髓中CFU-GM的数量明显受到抑制。使用LCM时，CFU-GM的数量始终高于重组鼠GM-CSF。这种可重复、定量的体外骨髓祖细胞培养系统是野生棉鼠骨髓毒性的敏感指标，可用于监测野生啮齿动物种群长期暴露于低水平环境毒物的情况。
