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Genotoxicity testing revealed that most new psychoactive substances (NPS), including phenethylamines like 2C-H and 2C-B, are genotoxic. These substances increase reactive oxygen species (ROS), highlighting potential long-term risks even at low doses.

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Area of Science:

  • Toxicology
  • Genetics
  • Pharmacology

Background:

  • New psychoactive substances (NPS), particularly phenethylamines, are increasingly prevalent.
  • Limited data exists on the genotoxic potential of these emerging substances.
  • Understanding genotoxicity is crucial for comprehensive risk assessment of NPS.

Purpose of the Study:

  • To evaluate the genotoxicity of selected phenethylamines (2C-H, 2C-I, 2C-B, 25B-NBOMe) and MDMA.
  • To investigate reactive oxygen species (ROS) induction as a potential mechanism of genotoxicity.
  • To fill the knowledge gap regarding the genotoxic effects of these NPS.

Main Methods:

  • TK6 cells were treated with varying concentrations (6.25-35 µM) of the selected substances.
  • Genotoxicity was assessed using the micronucleus (MN) assay.
  • Micronuclei (MNi) frequency was analyzed via an automated flow cytometric protocol.
  • Reactive oxygen species (ROS) levels were measured to explore the genotoxicity mechanism.

Main Results:

  • All tested phenethylamines, except MDMA, demonstrated significant genotoxic effects.
  • A statistically significant increase in ROS levels was observed for all genotoxic phenethylamines.
  • Cytotoxicity and cytostasis results informed the selection of appropriate concentrations for genotoxicity testing.

Conclusions:

  • The study confirms the genotoxic potential of several phenethylamine-based NPS.
  • ROS induction is identified as a likely mechanism underlying the observed genotoxicity.
  • Genotoxicity assessment is vital for a complete understanding of NPS risks, including potential long-term effects from seemingly safe doses.