Holden H E, Crider P A, Wahrenberg M G
Environ Mutagen. 1980;2(1):67-73. doi: 10.1002/em.2860020110.
Published reports have suggested the possible association of mutagenic or teratogenic properties of some benzimidazole analogs with induced spindle disruption and consequent mitotic arrest. Studies were conducted to explore this correlation. Seven benzimidazole analogs were evaluated in a human lymphocyte system for ability to block mitosis at metaphase. Confirming the previously reported results, four compounds, mebendazole, parbendazole, cambendazole, and fenbendazole, caused metaphase accumulation, which we found to be dose- and time-related. Minimum effective dose for mebendazole and cambendazole was 10 microgram/ml; for parbendazole, 1 microgram/ml; and for fenbendazole, 100 microgram/ml. The drug-induced mitotic arrest is qualitatively and quantitatively similar to that produced by colcemid. No activity was observed with three other compounds, benzimidazole, thiabendazole, and oxfendazole when tested at 100 microgram/ml. Presence of absence of mitotic effects is correlated with reported teratogenicity with five out of the seven analogs. This suggests some utility of mitotic assessments for predicting teratogenicity.
已发表的报告表明，某些苯并咪唑类似物的致突变或致畸特性可能与诱导纺锤体破坏及随后的有丝分裂停滞有关。开展了研究以探索这种相关性。在人类淋巴细胞系统中评估了七种苯并咪唑类似物在中期阻断有丝分裂的能力。证实了先前报道的结果，四种化合物，即甲苯咪唑、丙硫咪唑、坎苯达唑和芬苯达唑，导致中期积累，我们发现这与剂量和时间相关。甲苯咪唑和坎苯达唑的最小有效剂量为10微克/毫升；丙硫咪唑为1微克/毫升；芬苯达唑为100微克/毫升。药物诱导的有丝分裂停滞在质量和数量上与秋水仙酰胺产生的相似。当以100微克/毫升进行测试时，其他三种化合物，即苯并咪唑、噻苯达唑和奥芬达唑未观察到活性。七种类似物中有五种的有丝分裂效应的有无与报道的致畸性相关。这表明有丝分裂评估在预测致畸性方面有一定用途。
