title: Genotoxic properties of representatives of alkylindazoles and aminoalkyl-indoles which are consumed as synthetic cannabinoids.
abstract: Synthetic cannabinoids (SCs) cause similar effects as cannabis and are sold in herbal mixtures. Recent investigations indicate that some of these drugs possess genotoxic properties. Therefore, we tested representatives of two groups, namely, aminoalkylindoles (AM-2201 and UR-144) and 1-alkylindazoles (5F-AKB-48 and AM-2201-IC) in single cell gel electrophoresis and micronucleus (MN) assays with human lymphocytes and in Salmonella/microsome assays. All drugs except AM-2201 caused DNA-migration, the LOELs were between 50 and 75 µM. Furthermore, all SCs caused inhibition of cell division and significant induction of MN which reflect structural and numerical chromosomal aberrations. The LOEL values were 50 µM for UR-144 and 5-AKB-48 and 75 µM for the other drugs. Also the levels of nucleoplasmatic bridges which are formed from dicentric chromosomes were elevated under identical conditions while the frequencies of nuclear buds were not affected. These findings show that representatives of both groups cause chromosomal damage while the negative results in Salmonella assays (in strains TA98, TA100, TA1535, TA1537 and TA102) in absence and presence of metabolic activation indicate that they do not induce gene mutations. Taken together, these findings indicate that SCs may cause adverse health effects in users as a consequence of damage of the genetic material.
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
authors: Verena J
authors: VJ
authors: Koller
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
authors: Franziska
authors: F
authors: Ferk
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
authors: Halh
authors: H
authors: Al-Serori
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
authors: Miroslav
authors: M
authors: Mišík
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
authors: Armen
authors: A
authors: Nersesyan
authors: Institute of Forensic Medicine, Medical Center - University of Freiburg, Albertstraße 9, 79104 Freiburg, Germany.
authors: Volker
authors: V
authors: Auwärter
authors: German Federal Environmental Agency, Heinrich-Heine-Straße 12, 08645 Bad Elster, Germany.
authors: Tamara
authors: T
authors: Grummt
authors: Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria. Electronic address: siegfried.knasmueller@meduniwien.ac.at.
authors: Siegfried
authors: S
authors: Knasmüller
mesh_terms: D002186:Cannabinoids / Q000633:toxicity*; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000633:toxicity*; D007211:Indoles / Q000737:chemistry / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests
chemical_list: D002186:Cannabinoids; D007191:Indazoles; D007211:Indoles
keywords: Comet assay; Genotoxicity; Lymphocytes; Micronucleus; Synthetic cannabinoids