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Genetic toxicity of methamphetamine in vitro and in human abusers

Jih-Heng Li1, Heng-Cheng Hu, Wei-Bang Chen

  • 1National Bureau of Controlled Drugs, Department of Health, Taiwan, Republic of China. jhli@nbcd.gov.tw

Environmental and Molecular Mutagenesis
|December 16, 2003
PubMed

Insights

Methamphetamine (METH) is a genotoxic agent, causing DNA damage in lab cells and correlating with DNA damage markers in human METH abusers. Reactive oxygen species (ROS) may contribute to this methamphetamine-induced genotoxicity.

Area of Science:

  • Toxicology
  • Genetics
  • Neuroscience

Background:

  • Methamphetamine (METH) is a widely abused psychomotor stimulant.
  • Extensive research exists on METH-induced neurotoxicity.
  • The genotoxic potential of METH has remained largely unevaluated.

Purpose of the Study:

  • To investigate the genotoxicity of METH in vitro.
  • To assess METH's genotoxic effects in human METH abusers.

Main Methods:

  • Bacterial reverse mutation assay (Ames test) using Salmonella typhimurium strains TA98 and TA100.
  • In vitro genotoxicity assays in cultured Chinese hamster ovary K1 (CHO-K1) cells, including hprt mutation assay, micronucleus assay, and sister chromatid exchange (SCE) assay.
  • In vitro assays with rat liver S9 fraction and reactive oxygen species (ROS) scavengers.
  • Analysis of micronucleus and SCE frequencies in lymphocytes from human METH abusers and unexposed controls.

Main Results:

  • METH induced his(+) revertants in Salmonella typhimurium.
  • METH increased hprt mutants, micronuclei, and SCE frequency in CHO-K1 cells.
  • These effects were abolished by rat liver S9, indicating METH itself, not its metabolites, caused genotoxicity.
  • ROS scavengers inhibited METH-induced micronuclei formation.
  • Total METH exposure correlated with increased micronucleus and SCE frequencies in human lymphocytes.

Conclusions:

  • Methamphetamine (METH) is a genotoxic agent.
  • Reactive oxygen species (ROS) play a role in METH-induced genotoxicity.
  • Evidence suggests METH exposure poses a genotoxic risk to humans.

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