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使用单细胞凝胶电泳试验证明氯苯诱导的小鼠淋巴细胞DNA损伤。

Demonstration of chlorobenzene-induced DNA damage in mouse lymphocytes using the single cell gel electrophoresis assay.

作者信息

Vaghef H, Hellman B

机构信息

Department of Occupational and Environmental Medicine, University Hospital, Uppsala, Sweden.

出版信息

Toxicology. 1995 Jan 19;96(1):19-28. doi: 10.1016/0300-483x(94)02910-m.

Abstract

The DNA damaging effect of chlorobenzene was investigated in peripheral lymphocytes and bone marrow cells from C57BL/6 female mice using a gel electrophoresis assay for DNA from single cells ('the single cell gel electrophoresis assay') under alkaline conditions. The effect of chlorobenzene was studied both after single and repeated intraperitoneal injections of 750 mg/kg body weight. The cytostatic agent cyclophosphamide (150 mg/kg, i.p.) was used as a reference substance, and vehicle-treated mice as controls. DNA damage was recorded 16 h after the (last) injection, using an automated computerized image analysis system specifically designed for the single cell gel electrophoresis assay. There was evidence of chlorobenzene-induced DNA damage after 3 days of repeated exposure in peripheral lymphocytes, but no indications of such an effect in bone marrow cells. Cyclophosphamide induced significant damage to DNA both in bone marrow cells and lymphocytes, the effect being most pronounced in the latter cells. It is concluded that high-dose exposure to chlorobenzene is associated with genotoxicity to peripheral lymphocytes. However, this solvent is apparently not a major hazard to bone marrow cells, even after repeated high-dose exposure.

摘要

使用碱性条件下单细胞DNA凝胶电泳分析方法(“单细胞凝胶电泳分析”),研究了氯苯对C57BL/6雌性小鼠外周淋巴细胞和骨髓细胞的DNA损伤作用。分别在单次和重复腹腔注射750mg/kg体重氯苯后,对其效应进行了研究。将细胞抑制剂环磷酰胺(150mg/kg,腹腔注射)用作参考物质,将溶剂处理的小鼠作为对照。在(最后一次)注射后16小时,使用专门为单细胞凝胶电泳分析设计的自动化计算机图像分析系统记录DNA损伤情况。重复暴露3天后,有证据表明氯苯在外周淋巴细胞中可诱导DNA损伤,但在骨髓细胞中未发现这种效应的迹象。环磷酰胺在骨髓细胞和淋巴细胞中均诱导了显著的DNA损伤,在后者细胞中效应最为明显。得出的结论是,高剂量暴露于氯苯与外周淋巴细胞的遗传毒性有关。然而,即使在重复高剂量暴露后,这种溶剂显然对骨髓细胞不是主要危害。

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