Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo
Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo
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DOI：
10.1016/s0378-4274(02)00057-7
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发表时间：
2002-06-14
影响因子：
3.5
通讯作者：
Molina, D
中科院分区：
文献类型：
--
作者：
Paniagua-Pérez, R;Madrigal-Bujaidar, E;Molina, D
丙咪嗪和地昔帕明是两种广泛使用的三环类抗抑郁药，但在体外遗传毒性评价方面却显示出相互矛盾的结果。这项研究的目的是确定这些化合物在体内诱导小鼠骨髓细胞姐妹染色单体交换(SCES)的能力。对于每个院落，动物被分成五组，由五个人组成。分别给予阴性对照组0.4ml蒸馏水、阳性对照组环磷酰胺70 mg/kg、丙咪嗪7、20、60 mg/kg组和地塞帕明2、20、60 mg/kg组。小鼠皮下注射5-溴脱氧尿苷片(45 Mg)，1h后给药。片剂植入21h后给予秋水仙碱，3h后取股骨骨髓在KCL中固定，Hoechst-Giemsa法染色。结果表明，从第二次试验剂量开始，两种化合物均为姐妹染色单体互换诱导剂。这些化合物的反应是剂量依赖的，并表明最高测试剂量增加了大约四倍的姐妹染色单体交换控制水平。药物对细胞增殖动力学无明显影响，最高剂量组细胞分裂指数略有下降。这些结果表明这两种化合物在体内具有遗传毒性潜力，并表明在其他模型中对它们的评估是相关的。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
Imipramine and desipramine are two widely used tricyclic antidepressants which have shown conflicting results in regard to their in vitro genotoxic evaluation. The aim of this investigation was to determine the capacity of these compounds to induce in vivo sister-chromatid exchanges (SCEs) in mouse bone marrow cells. For each compound, the animals were organized in five groups constituted by five individuals. They were intraperitoneally (ip) administered with the test substances as follows: a negative control group treated with 0.4 ml of distilled water, a positive control group administered with cyclophosphamide (70 mg/kg), three-groups treated with imipramine (7, 20 and 60 mg/kg), and three other groups treated with desipramine (2, 20 and 60 mg/kg). The general procedure included the subcutaneous implantation to each mouse of a 5-bromodesoxyuridine tablet (45 mg), and I h later, the administration of the chemicals involved. Twenty-one hours after the tablet implantation, the mice received colchicine, and 3 h later their femoral bone marrow was obtained in KCL, fixed, and stained with the Hoechst-Giemsa method. The results showed that both compounds were SCE inducers, starting from the second tested dose. The response of these compounds was dose-dependent, and showed that the highest tested dose increased about four times the SCE control level. The cellular proliferation kinetics was not affected by the chemicals, and the mitotic indexes were slightly diminished with the highest dose. These results indicate an in vivo genotoxic potential for both chemicals, and suggest that it is pertinent to follow their evaluation in other models. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.