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首页> 外文期刊>Mutation Research, E. Environmental Mutagenesis and Related Subjects >An in vivo/in vitro method for assessing micronucleus and chromosome aberration induction in rat bone marrow and spleen 1. Studies with cyclophosphamide
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An in vivo/in vitro method for assessing micronucleus and chromosome aberration induction in rat bone marrow and spleen 1. Studies with cyclophosphamide

机译：一种评估大鼠骨髓和脾脏微核和染色体畸变诱导的体内/体外方法1.环磷酰胺的研究

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The mouse micronucleus assay has long been used as an indicator of in vivo genotoxicity. Recently, it was shown that no single protocol is adequate to detect all clastogens. As a first step in developing a potentially more sensitive assay, micronucleus induction by cyclophosphamide (CP) was assessed in an in vivo/in vitro system using rat bone marrow and spleen cells. In each of two independent experiments, two rats/dose were treated i.p. with 0, 20, or 40 mg CP/kg and killed 6 h later. Cultures werethen established in the presence of growth stimulants (interleukin-3 and granuiocyte-macrophage colony stimulating factor for bone marrow; lipopolysaccharide and concanavalin A for spleen) and cytochalasin B, a cytokinesis inhibitor. Bone marrow cells were harvested and slides prepared 24 h after initiation, while spleen cells were harvested at 48 h. One thousand cells/tissue/group were scored for cell cycle kinetics and 1000 binucleate (BN) cells were scored for micronuclei. In addition, spleen cellswere concurrently assayed for chromosome aberrations. A dose-related cell cycle delay was observed in both tissues in both experiments. Bone marrow showed a 6% average background frequency of micronucleated BN cells, while the low dose induced an averageof 20%, and the high dose 31%. For spleen, the average control frequency of micronucleated BN cells was 3%, the low dose induced a 40% average frequency, and the high dose 65%. Also in splenocytes, a dose-dependent increase in chromosome aberrations wasobserved, with an almost 40-fold increase observed over the control value at the high dose. Thus, the in vivo/in vitro approach described here shows great potential in detecting drug induced genotoxicity. Also, spleen appears more sensitive than bone marrow to CP.
机译：小鼠微核试验长期以来一直用作体内遗传毒性的指标。最近，显示出没有单一的协议足以检测所有克拉斯多菌。作为开发可能更敏感的测定方法的第一步，使用大鼠骨髓和脾细胞在体内/体外系统中评估了环磷酰胺（CP）诱导的微核。在两个独立实验的每一个中，腹膜内处理两只大鼠/剂量。剂量为0、20或40 mg CP / kg，6小时后杀死。然后在生长刺激物（白细胞介素3和粒细胞巨噬细胞集落刺激因子对骨髓;脂多糖和伴刀豆球蛋白A对脾脏）和细胞松弛素B（一种细胞分裂抑制剂）的存在下建立培养物。起始后24小时收获骨髓细胞并制备载玻片，而在48小时收获脾细胞。对1,000个细胞/组织/组的细胞周期动力学进行评分，并对1000个双核（BN）细胞的微核进行评分。另外，同时测定脾细胞的染色体畸变。在两个实验中，在两个组织中均观察到剂量相关的细胞周期延迟。骨髓显示微核BN细胞的平均本底频率为6％，而低剂量诱导的平均背景频率为20％，高剂量诱导的平均背景频率为31％。对于脾脏，微核BN细胞的平均控制频率为3％，低剂量诱导的平均频率为40％，高剂量诱导的65％。同样在脾细胞中，观察到染色体畸变的剂量依赖性增加，在高剂量下观察到的比对照值增加了近40倍。因此，本文所述的体内/体外方法显示出检测药物诱导的基因毒性的巨大潜力。而且，脾脏对CP的敏感性似乎比骨髓更敏感。

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