Koller Verena J, Ferk Franziska, Al-Serori Halh, Mišík Miroslav, Nersesyan Armen, Auwärter Volker, Grummt Tamara, Knasmüller Siegfried
Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
Institute of Forensic Medicine, Medical Center - University of Freiburg, Albertstraße 9, 79104 Freiburg, Germany.
Food Chem Toxicol. 2015 Jun;80:130-136. doi: 10.1016/j.fct.2015.03.004. Epub 2015 Mar 16.
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.
合成大麻素（SCs）产生与大麻相似的效果，并以草药混合物的形式出售。最近的调查表明，其中一些药物具有遗传毒性。因此，我们使用人类淋巴细胞，通过单细胞凝胶电泳和微核（MN）试验以及沙门氏菌/微粒体试验，对两组药物的代表物进行了测试，即氨基烷基吲哚（AM - 2201和UR - 144）和1 - 烷基吲唑（5F - AKB - 48和AM - 2201 - IC）。除AM - 2201外，所有药物均导致DNA迁移，最低观察到有害作用水平（LOELs）在50至75μM之间。此外，所有合成大麻素均导致细胞分裂抑制和微核的显著诱导，这反映了结构和数量染色体畸变。UR - 144和5 - AKB - 48的LOEL值为50μM，其他药物为75μM。在相同条件下，由双着丝粒染色体形成的核质桥水平也升高，而核芽频率未受影响。这些发现表明，两组药物的代表物均会导致染色体损伤，而在有无代谢活化的情况下，沙门氏菌试验（在TA98、TA100、TA1535、TA1537和TA102菌株中）的阴性结果表明它们不会诱导基因突变。综上所述，这些发现表明，合成大麻素可能因遗传物质受损而对使用者造成不良健康影响。
