Intense oxidative DNA damage promoted by L-dopa and its metabolites. Implications for neurodegenerative disease

FEBS Lett. 1994 Oct 24;353(3):246-50. doi: 10.1016/0014-5793(94)01056-0.

Abstract

Oxidative DNA damage can cause mutation and cell death. We show that L-DOPA, dopamine and 3-O-methyl-DOPA cause extensive oxidative DNA damage in the presence of H2O2 and traces of copper ions. 8-Hydroxyguanine is the major product. Iron ions were much less effective and manganese ions did not catalyse DNA damage. We propose that copper ion release, in the presence of L-DOPA and its metabolites, may be an important mechanism of neurotoxicity, e.g. in Parkinson's disease and amyotrophic lateral sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Chemistry
  • Catalysis
  • Copper / analysis
  • Copper / toxicity*
  • DNA / drug effects*
  • DNA Damage*
  • Dopamine / pharmacology
  • Humans
  • Hydrogen Peroxide
  • Iron / analysis
  • Iron / toxicity
  • Levodopa / pharmacology*
  • Oxidation-Reduction
  • Parkinson Disease / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology

Substances

  • Tyrosine
  • Levodopa
  • Copper
  • DNA
  • Hydrogen Peroxide
  • Iron
  • 3-methoxytyrosine
  • Dopamine