Mitotic arrest by benzimidazole analogs in human lymphocyte cultures

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.