PMID- 33348640 OWN - NLM STAT- MEDLINE DCOM- 20210315 LR - 20210315 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 24 DP - 2020 Dec 17 TI - Novel Psychoactive Phenethylamines: Impact on Genetic Material. LID - 10.3390/ijms21249616 [doi] LID - 9616 AB - Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and the popular 3,4-Methylenedioxymethylamphetamine (MDMA). On the basis of cytotoxicity and cytostasis results, we selected the concentrations (6.25-35 microM) to be used in genotoxicity analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by an automated flow cytometric protocol. All substances, except MDMA, resulted genotoxic; therefore, we evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the demonstrated genotoxicity. The obtained results showed a statistically significant increase in ROS levels for all genotoxic phenethylamines confirming this hypothesis. Our results highlight the importance of genotoxicity evaluation for a complete assessment of the risk associated also with NPS exposure. Indeed, the subjects who do not have hazardous behaviors or require hospitalization by using active but still "safe" doses could run into genotoxicity and in the well-known long-term effects associated. FAU - Cocchi, Veronica AU - Cocchi V AUID- ORCID: 0000-0002-0958-3615 AD - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy. FAU - Gasperini, Sofia AU - Gasperini S AD - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy. FAU - Hrelia, Patrizia AU - Hrelia P AUID- ORCID: 0000-0002-8415-3711 AD - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy. FAU - Tirri, Micaela AU - Tirri M AUID- ORCID: 0000-0001-9337-9184 AD - Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy. FAU - Marti, Matteo AU - Marti M AD - Department of Translational Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy. AD - Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, Presidency of the Council of Ministers, 44121 Ferrara, Italy. FAU - Lenzi, Monia AU - Lenzi M AD - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy. LA - eng GR - Effects of NPS: development of a multicentre research for the information enhancement of the Early Warning System, M.Marti/Anti-Drug Policies Department, Presidency of the Council of Ministers, Italy/ PT - Journal Article DEP - 20201217 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anisoles) RN - 0 (Dimethoxyphenylethylamine) RN - 0 (Hallucinogens) RN - 0 (Phenethylamines) RN - 0 (Psychotropic Drugs) RN - 0 (Reactive Oxygen Species) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - S35362848V (4-iodo-2,5-dimethoxy-beta-phenethylamine) RN - S6NAA81PHK (2-(4-bromo-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine) RN - V77772N32H (2-(4-bromo-2,5-dimethoxyphenyl)ethylamine) SB - IM MH - Anisoles/*pharmacology MH - Apoptosis/drug effects MH - Cell Line MH - Cell Survival/drug effects MH - Dimethoxyphenylethylamine/*analogs & derivatives/pharmacology MH - Flow Cytometry/methods MH - Genes/*drug effects MH - Hallucinogens/pharmacology MH - Humans MH - Micronuclei, Chromosome-Defective/chemically induced MH - Micronucleus Tests/methods MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Phenethylamines/*pharmacology MH - Psychotropic Drugs/*pharmacology MH - Reactive Oxygen Species/analysis/metabolism PMC - PMC7766159 OTO - NOTNLM OT - 25B-NBOMe OT - 2C-B OT - 2C-H OT - 2C-I OT - MDMA OT - ROS OT - flow cytometry OT - genotoxicity OT - phenethylamine COIS- The authors declare no conflict of interest. EDAT- 2020/12/23 06:00 MHDA- 2021/03/16 06:00 PMCR- 2020/12/17 CRDT- 2020/12/22 01:03 PHST- 2020/11/05 00:00 [received] PHST- 2020/12/04 00:00 [revised] PHST- 2020/12/15 00:00 [accepted] PHST- 2020/12/22 01:03 [entrez] PHST- 2020/12/23 06:00 [pubmed] PHST- 2021/03/16 06:00 [medline] PHST- 2020/12/17 00:00 [pmc-release] AID - ijms21249616 [pii] AID - ijms-21-09616 [pii] AID - 10.3390/ijms21249616 [doi] PST - epublish SO - Int J Mol Sci. 2020 Dec 17;21(24):9616. doi: 10.3390/ijms21249616.