不同剂量环磷酰胺诱发NIH小鼠骨髓红细胞微核率的比较

Comparison of erythrocyte micronuclei frequency in NIH mouse thigh-bone marrow induced by different doses of cyclophosphamide

目的探讨环磷酰胺（CP）不同剂量、不同取材时间对NIH小鼠骨髓红细胞微核率的影响。方法对小鼠一次性腹腔注射不同剂量的CP（25、50、100mg/kg.BW）后,于不同时间（给药后12、18、24、36、48、72h）取材股骨制作骨髓涂片,观察CP对NIH小鼠骨髓红细胞微核率的影响。结果高、中、低3个剂量组的小鼠骨髓红细胞微核率与溶剂对照组相比较,其差异具有统计学意义（P〈0.05）,且3个剂量组之间两两比较差异均有统计学意义（P〈0.05）,并表现出明显的剂量-反应关系;不同取样时间对小鼠骨髓细胞微核率的影响具有统计学意义（P〈0.05）。本实验室条件下,给NIH小鼠一次性腹腔注射CP后12~48h股骨取材均可取得较高的微核率,其中以24h微核率最高。结论CP作为微核试验的阳性对照其剂量范围为50~100mg/kg.BW,给药后24h取材最佳,给药12~48h股骨取材均可获得较高的微核率。

Objective To explore effect of different doses of cyclophosphamide（CP）and sampling time on erythrocyte micronucleus frequency in NIH mouse thigh-bone marrow.Methods Mice were injected intraperitoneally with different single dose of CP（25,50,100mg/kg·BW）,then femoral marrow from mice were obtained at different time（after the administration of 12th,18th,24th,36th,48th,72nd h） and marrow slides were made.Changes of erythrocyte micronuclei frequency that CP induced on NIH mouse thigh-bone marrow were observed.Results Compared to the control group,significant difference of erythrocytes micronucleus frequency was found in mice thigh-bone marrow among three groups（high dose group,middle dose group and low dose group）（P〈0.05）.It was showed that statistically significance exited（P〈0.05） between any two of three dose groups,demonstrating a clear dose-response relationship.Also there was statistical significance（P〈0.05） in erythrocyte micronucleus frequency in mice thigh-bone marrow obtained at different sampling time.25,50,100mg/kg·BW cyclophosphamide might lead to increasing of erythrocyte micronuclei frequency in NIH mice thigh-bone marrow under our laboratory conditions,showing a dose-response relationship and a time-effect relationship in a certain range of dose.High micronucleus frequency was obtained when femoral bones from mice were taken 12 ~ 48h after injection of cyclophosphamide into mice.Maximum of micronucleus frequency was got 24h after injection.Conclusion It was optimal that when dose range of CP,as a positive control,was 50-100mg/kg·BW,and especially 24h after administration,and high micronucleus rate 12-48h after injection CP can be obtained.