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

Abstract

Low passage-number cultured Chinese hamster cells were used to assess the ability of four benzodiazepines, namely diazepam, medazepam, midazolam and bromazepam, to induce numerical and structural chromosome aberrations. It was observed that diazepam, medazepam and midazolam treatment produced dose-dependent reductions in the number of diploid cells, with medazepam and midazolam inducing significant levels of hyperdiploidy and diazepam inducing low levels of hypodiploidy (at toxic doses). In contrast, bromazepam-treated cultures showed no significant changes in the level of aneuploidy even when exposed to toxic concentrations. All four sedatives were seen to induce low levels of chromosome aberrations, with bromazepam showing the most potent effect (albeit at a single toxic dose). These observations indicate that these structurally related benzodiazepines could be regarded as potentially genotoxic.