Madrigal-Bujaidar E, Velazquez-Guadarrama N, Morales-Ramirez P, Mendiola M T, Martínez A L, Chamorro G
Laboratorio de Genética, Escuela Nacional de Ciencias Biológicas, I.P.N., México, D.F.
Food Chem Toxicol. 1999 Jul;37(7):757-63. doi: 10.1016/s0278-6915(99)00061-7.
Disulfiram is a widely used drug to treat alcoholism due to its capacity to inhibit the metabolism of acetaldehyde; however, its genotoxic potential is not well known. Thus, the aim of this investigation was to determine whether the chemical may induce sister-chromatid exchanges (SCEs) in an in vivo study using mouse bone marrow and spermatogonial cells. We used doses of 200, 400 and 800 mg/kg body weight and compared the obtained data with the values determined in a negative control group as well as with a positive control group (cyclophosphamide, 50 mg/kg). The results in both systems indicated a weak genotoxic response by the chemical. In the case of bone marrow, a significant SCE level was achieved only with the high tested dose, but in spermatogonial cells the three doses tested showed a significant difference with respect to the negative control. No significant alterations in the mitotic index or in the cell proliferation kinetics were observed in somatic cells. Concerning the effect of cyclophosphamide, an increase in the level of SCEs was observed in both types of cells, reaching more than three times the values obtained in their respective control groups.
双硫仑是一种广泛用于治疗酒精中毒的药物，因其能够抑制乙醛的代谢；然而，其遗传毒性潜力尚不清楚。因此，本研究的目的是在一项使用小鼠骨髓和精原细胞的体内研究中确定该化学物质是否会诱导姐妹染色单体交换（SCE）。我们使用了200、400和800mg/kg体重的剂量，并将获得的数据与阴性对照组以及阳性对照组（环磷酰胺，50mg/kg）确定的值进行比较。两个系统的结果均表明该化学物质具有较弱的遗传毒性反应。在骨髓中，仅在高测试剂量下才达到显著的SCE水平，但在精原细胞中，测试的三个剂量与阴性对照相比均显示出显著差异。在体细胞中未观察到有丝分裂指数或细胞增殖动力学的显著变化。关于环磷酰胺的作用，在两种类型的细胞中均观察到SCE水平升高，达到各自对照组所获值的三倍以上。
