Carballo M A, Hick A S, Soloneski S, Larramendy M L, Mudry M D
Citogenética y Genética Toxicológica. Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
J Appl Toxicol. 2006 Jul-Aug;26(4):293-300. doi: 10.1002/jat.1132.
To contribute to a more accurate characterization of the mutagenic and aneugenic effects of thiabendazole (TBZ), a widely used antiparasitic and food preservative drug, the induction of sister chromatid exchanges (SCEs) and mitotic spindle anomalies as cytogenetic end-points were investigated. Studies were carried out in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. A significant dose-dependent increase in SCE frequency was observed in CHO cells with S9-Mix (P < 0.01) in the 50-100 microg ml(-1) dose-range, while in the absence of S9-Mix, an enhancement of the SCE frequency was exhibited at the highest dose (P < 0.01). In CHO-K1 cells a significant increase in mitotic spindle anomalies (P < 0.01) was observed with the highest concentration assayed reflecting the specific effect of TBZ formulation at the microtubule level. Cell proliferation kinetics (CPK) were not modified by the addition of this pharmaceutical product. In human lymphocyte cultures, exposure to 100 microg ml(-1) TBZ formulation resulted in a significant decrease of the mitotic index (MI) (P < 0.003) and changes in the replication index (RI) (P < 0.05).
为了更准确地表征噻苯达唑（TBZ）的诱变和非整倍体效应，TBZ是一种广泛使用的抗寄生虫和食品防腐剂药物，研究了作为细胞遗传学终点的姐妹染色单体交换（SCE）和有丝分裂纺锤体异常的诱导情况。研究在中国仓鼠卵巢（CHO）细胞和人外周血淋巴细胞中进行。在50 - 100μg/ml剂量范围内，使用S9混合物时，CHO细胞中观察到SCE频率有显著的剂量依赖性增加（P < 0.01），而在没有S9混合物的情况下，在最高剂量时SCE频率有所增加（P < 0.01）。在CHO - K1细胞中，在所检测的最高浓度下观察到有丝分裂纺锤体异常显著增加（P < 0.01），反映了TBZ制剂在微管水平的特定作用。添加该药物产品未改变细胞增殖动力学（CPK）。在人淋巴细胞培养物中，暴露于100μg/ml的TBZ制剂导致有丝分裂指数（MI）显著降低（P < 0.003）和复制指数（RI）发生变化（P < 0.05）。
