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 treatment of various psychiatric disorders. One member of this class, oxazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is inconsistent, we investigated the oxazepam-induced formation of micronuclei in Syrian Hamster embryo fibroblast (SHE) cells, human amniotic fluid fibroblast-like (AFFL) cells and L5178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all three cell lines. The time course of micronucleus induction in L5178Y cells 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 kinetochores in approximately 50% of the micronuclei in all three cell types. This result was further confirmed by in situ hybridization in L5178Y cells and indicates the presence of whole chromosomes or centric fragments as well as acentric fragments in the oxazepam-induced micronuclei. The L5178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used.
Stopper
H
H
Institute of Pharmacology and Toxicology, University of Würzburg, FRG.
Körber
C
C
Spencer
D L
DL
Kirchner
S
S
Caspary
W J
WJ
Schiffmann
D
D
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004276:DNA, Satellite / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D006801:Humans; D007739:L Cells; D008647:Mesocricetus; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000737:chemistry / Q000648:ultrastructure; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage*; D010076:Oxazepam / Q000008:administration & dosage / Q000633:toxicity*
D004276:DNA, Satellite; D009153:Mutagens; D010076:Oxazepam