Methamphetamine ("crystal meth") causes induction of DNA damage and chromosomal aberrations in human derived cells.

Abstract

Methamphetamine (METH) is a widely consumed psychostimulant drug; its acute toxic effects in brain and liver are well known, furthermore, there is some evidence in regard to its DNA damaging properties in humans. Therefore, we studied the impact of the drug on genomic stability in human derived hepatoma (HepG2) cells, which reflect the activation/detoxification of drugs better than other cell lines. Furthermore, experiments with human buccal derived cells (TR146) were conducted as the drug is consumed orally. Induction of DNA damage in both cell types with doses reflecting the exposure in abusers was found in single cell gel electrophoresis (SCGE) assays (which detect single and double strand breaks as well as apurinic sites). Furthermore, induction of micronuclei (formed as a consequence of structural and numerical chromosomal aberrations) and formation of nuclear buds resulting from gene amplifications was detected. Additional experiments with lesion-specific enzymes showed that the drug causes oxidation of purines and pyrimidines, indicating that its genotoxic effects may be due to oxidation of the DNA. Our findings support the assumption that the drug may cause adverse health effects (such as cancer and infertility) in long-term users which are causally related to DNA damage.

• Authors: Nathalie Ropek, Halh Al-Serori, Miroslav Mišík, Armen Nersesyan, Harald H Sitte, Andrew R Collins, Sergey Shaposhnikov, Siegfried Knasmüller, Michael Kundi, Franziska Ferk
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 128 Pg. 1-7 (Jun 2019) ISSN: 1873-6351 [Electronic] England
• PMID: 30910685 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Mutagens
• Methamphetamine
• DNA
• Endodeoxyribonucleases
• DNA-Formamidopyrimidine Glycosylase

Topics

• Amphetamine-Related Disorders (blood)
• Cell Line
• Chromosome Aberrations
• Comet Assay (methods)
• Cytokinesis (drug effects)
• DNA (drug effects, metabolism)
• DNA Damage
• DNA-Formamidopyrimidine Glycosylase (metabolism)
• Dose-Response Relationship, Drug
• Endodeoxyribonucleases (metabolism)
• Hep G2 Cells
• Humans
• Methamphetamine (administration & dosage, toxicity)
• Micronucleus Tests
• Mutagens (administration & dosage, toxicity)
• Oxidation-Reduction
• Toxicity Tests, Acute