A study of the induction of aneuploidy and chromosome aberrations after diazepam, medazepam, midazolam and bromazepam treatment

Low passage-number cultured Chinese hamster cells were usedto assess the ability of four benzodiazepines, namely diazepam,medazepam, midazolam and bromazepam, to induce numerical andstructural chromosome aberrations. It was observed that diazepam,medazepam and midazolam treatment produced dose-dependent reductionsin the number of diploid cells, with medazepam and midazolaminducing significant levels of hyperdiploidy and diazepam inducinglow levels of hypodiploidy (at toxic doses). In contrast, bromazepam-treatedcultures showed no significant changes in the level of aneuploidyeven when exposed to toxic concentrations. All four sedativeswere seen to induce low levels of chromosome aberrations, withbromazepam showing the most potent effect (albeit at a singletoxic dose). These observations indicate that these structurallyrelated benzodiazepines could be regarded as potentially genotoxic.