Genotoxicity evaluation of five tricyclic antidepressants in the wing somatic mutation and recombination test in Drosophila melanogaster.
Five tricyclic antidepressants were tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Three-day-old larvae trans-heterozygous for 2 linked recessive wing hair mutants (multiple wing hairs and flare) were fed the test compounds in water mixed with a standard dry food for 48 h. Wings of the emerging adult flies were scored for the presence of spots of mutant cells which can be the consequence of either somatic mutation or mitotic recombination. Desipramine and imipramine were clearly genotoxic at concentrations above 1 mM whereas amitriptyline, nortriptyline and protriptyline were not genotoxic at concentrations up to 100 mM. This seems to implicate the nitrogen atom at position 5 in the 7-membered ring of the tricyclic molecule as being responsible for the genotoxic property of the compounds in Drosophila.
van Schaik
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N
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach, Switzerland.
Graf
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U
D000639:Amitriptyline / Q000633:toxicity; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D003891:Desipramine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D007099:Imipramine / Q000633:toxicity; D009152:Mutagenicity Tests; D009661:Nortriptyline / Q000633:toxicity; D011530:Protriptyline / Q000633:toxicity; D011995:Recombination, Genetic
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D011530:Protriptyline; D004247:DNA; D009661:Nortriptyline; D007099:Imipramine; D003891:Desipramine