Intense oxidative DNA damage promoted by l-DOPA and its metabolites implications for neurodegenerative disease

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 H 2O 2 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.