AN INVESTIGATION OF MICRONUCLEUS AND MUTATION-INDUCTION BY OXAZEPAM IN MAMMALIAN-CELLS

The benzodiazepines are a class of drugs that are widely used in the t reatment of various psychiatric disorders. One member of this class, o xazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properti es of these compounds is inconsistent, we investigated the oxazepam-in duced formation of micronuclei in Syrian Hamster embryo fibroblast (SH E) cells, human amniotic fluid fibroblast-like (AFFL) cells and L5178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all three celt lines. The time course of micronucleus inducti on in L5178Y celts showed a maximum at 5 h after treatment, suggesting that the micronuclei were formed in the first mitosis after treatment . Kinetochore staining (CREST-antiserum) revealed the presence of kine tochores in approximately 50% of the micronuclei in all three cell typ es. This result was further confirmed by in situ hybridization in L517 8Y cells and indicates the presence of whole chromosomes or centric fr agments as well as acentric fragments in the oxazepam-induced micronuc lei. The L5178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used.