Genotoxic properties of two synthetic cathinones (commonly used as psychoactive drugs).

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• Created: Thursday, 06 October 2016 14:02

A team of scientists from the Institute of Cancer Research (Medical University of Vienna) and the Institute of Forensic Medicine (University of Freiburg) have worked together in collaboration to investigate the potential harmful effects of synthetic cathinones (SCAs). 

According to the literature, SCAs are consumed worldwide as psychostimulants and are increasingly marketed as surrogates of classical illicit drugs via the internet.  Alarmingly, it is reported that the genotoxic properties of these drugs have not been investigated. However, results of earlier studies show that amphetamines which are structurally closely related to these compounds cause damage to the genetic material. Therefore, the researchers from the two universities decided to investigate this area.  They used a panel of genotoxicity tests to investigate the genotoxic properties of two widely consumed SCAs:

•         3-MMC (2-(methylamino)-1-(3-methylphenyl) propan-1-one)
•         4-MEC (2-(ethylamino)-1-(4-methylphenyl) propan-1-one)

The scientists found no evidence for induction of gene mutations in Salmonella/microsome assays, but both drugs caused positive results in the single cell gel electrophoresis (SCGE or comet) assay.  For the comet assay, they chose to use a human derived buccal cell line (TR146).  Air-dried slides were stained with propidium iodide and the percentage of DNA in the tails was measured by use of a computer aided image analysis system (Comet IV, Perceptive Instruments Ltd, Bury St Edmunds, UK).  Full experimental details can be found in the publication.   

Results:

•        3-MMC induced similar effects as 4-MEC and also caused significant induction of micronuclei which are formed as a consequence of structural and chromosomal aberrations.
•        Negative results obtained in SCGE experiments (comet assay) with lesion specific enzymes (FPG and Endo III) show that these drugs do not cause oxidative damage of DNA.
•        Moderate induction of TBARS (which leads to the formation of DNA-reactive substances) was observed with 4-MEC, indicating that the drug causes lipid peroxidation while no clear effect was detected with 3-MMC.
•        Results obtained with liver homogenate in SCGE-experiments (comet assay) show that phase I enzymes do not lead to the formation of DNA reactive metabolites.

The scientists concluded, based on all their findings, that consumption of certain SCAs may cause adverse health effects in users as a consequence of damage to the genetic material.

For more information on this investigation, please refer to the original publication:
Investigations of the genotoxic properties of two synthetic cathinones (3-MMC, 4-MEC) which are used as psychoactive drugs Halh Al-Serori, Franziska Ferk, Verena Angerer, Miroslav Mišík, Armen Nersesyan, Tahereh Setayesh, Volker Auwärter, Elisabeth Haslinger, Wolfgang Huberand Siegfried Knasmüller