环磷酰胺与异环磷酰胺对小鼠骨髓及胎肝微核率的影响

EFFECT OF CYCLOPHOSPHAMIDE AND IFOSFAMIDE ON THE FREQUENCIES OF MICRONUCLEUS IN PREGNANCY MICE

目的与方法 :本文研究了受孕小鼠尾静脉注射环磷酰胺 (CP)和异环磷酰胺 (IFO)对母鼠骨髓和胎肝微核频率及嗜多染红细胞与正成红细胞比率 (PCE/NCE)的影响。结果 :CP和IFO分别在 5mg/kg .bw时均不诱发母鼠骨髓、胎肝微核率升高和PCE/NCE比率显著变化。当剂量升高至 15mg/kg .bw时 ,CP和IFO诱发骨髓微核率分别为 15 .40± 3.0 5‰和 12 .2 0± 3.5 6‰ ,诱发胎肝微核率分别为 2 3.6 0± 3.6 5‰和 2 1.0 0± 5 .15‰ ,与对照组比较均有显著差别 (P <0 .0 5 )。当剂量为 30mg/kg .bw时 ,微核率升高更显著 ,有明显剂量—效应关系。两药在诱发微核的剂量条件下 ,均可使骨髓和胎肝PCE/NCE比率呈剂量依赖性下降。同等剂量条件下 ,两药对胎肝的作用均明显强于各自对骨髓的作用 ,但IFO对两种组织微核率及PCE/NCE的影响均轻于CP对相应组织的作用。结论 :鉴于CP和IFO都可进入骨髓和透过胎盘屏障引起染色体损伤 ,提示对生产和操作人员应采取必要的防护措施 ;对临床使用的患者要密切监测两者的毒副作用。

Purpose and Methods: The frequencies of micronucleus in polychromatic erythrocytes as well as the PCE/NCE ratios in maternal bone marrow and in fetal liver induced by Cyclophsphamide(CP) and Ifosfamide(IFO) were studied in pregnancy mice. Results: The results suggested that the micronucleus frequencies in maternal bone marrow and in fetal liver did not change significantly compared to the control group at the dose of 5mg/kg.bw CP and IFO respectively. So were the PCE/NCE ratios in both tissues. When the doses were raised to 15mg/kg.bw , the micronucleus frequencies were 15.40±3.05‰ and 12.20±3.56‰ in maternal bone marrow, 23.60±3.65‰ and 21.00±5.15‰ in fetal liver for CP and IFO respectively, both were significantly different from control group at P<0.05. When the doses were 30mg/kg.bw, the micronucleus frequencies in both tissues increased more significantly, showing obvious dose-response relations. At the doses that inducing the increase of micronucleus frequencies of both drugs, the PCE/NCE ratios declined dose-dependently in the two tissues. Both drugs showed greater genotoxicity respectively in fetal liver than in maternal bone marrow at the same dose. However, CP was more effective than IFO in the same tissue at the same dose. Conclusion: We concluded that CP and IFO could not only go into bone marrow but also go through placental barrier to induce chromosome damage. Thus protection for the workers producing or operating CP and IFO against the genotoxicity of the two drugs was necessary; the clinical toxicity and side effect of both drugs to patients should be inspected periodically.