环磷酰胺诱导小鼠骨髓细胞微核的影响因素的研究

STUDY ON THE INFLUENTIAL FACTORS OF INDUCING THE MICRONUCLEUS FREQUENCY OF MOUSE BONE MARROW BY CYCLOPHOSPHAMIDE

[目的]研究环磷酰胺(Cyclophosphamide,CP)诱导小鼠骨髓细胞微核的影响因素,确定其在经口试验中作为阳性对照使用最佳组合。[方法]小鼠一次性经口给于CP40、80mg/kg的剂量后,分别在不同的时间、不同的部位采取骨髓,观察骨髓细胞的微核率,同时观察嗜多染红细胞(PCE)和正染红细胞(NCE)的比值。[结果]小鼠在给予40mg/kg和80mg/kg CP后的骨髓微核率随取样时间的变化趋势是一致的。而给药组PCE与NCE比值与对照组的比较差异均无统计学意义,对骨髓细胞无明显抑制作用。但80mg/kg微核率显著高于40mg/kg剂量组,表明有一定剂量反应关系。但48h采取的骨髓的微核率与24h、30h有明显下降的趋势。[结论]环磷酰胺可用作微核试验的阳性对照物。其经口的剂量范围在40～80mg/kg,采集样本的时间应在给药后24～30h。胸骨髓是微核试验的最好材料。

[Objective] To study the influential factors of inducing micronucleus （MN） frequency of mouse bone marrow by cyclophosphamide （CP）, and decide the best combination of factors in orally for CP as positive control agent in MN test. [ Methods] After the mouse were single orally treated by cp of 40, 80 mg/kg, the micronucleus frequencies of mouse bone marrow, as well as the PCE/NCE ratios were explored at sampling time, and different parts. [Results] The changing trends of the micronucleus frequencies in PCE in the two groups receiving 40 mg/kg and 80 mg/kg of CP were the same at different sampiing times. The ratios of PCE to NCE of the two treated groups were not significantly different from the control group. This indicated that the mice bone marrow cells were not suppressed by one CP Of 40 or 80 mg/kg by orally. The micronucleus frequency in PCE of 40 mg/kg was significantly different from that of 80 mg/kg, showing a dose-response relationship. The decrease at 48h made remarkable differences from that of at 24 h and 30 h. The frequency of the chest bone marrow was slightly higher than that of thigh bone. [Conclution] CP can be used as a positive control of micronucleus test. The dose range of 40-80 mg/kg was appropiate, and the optimal sampling time is 24 h after treatment. The chest bone marrow is the best material in the micronucleus test.