Intense oxidative DNA damage promoted by L-dopa and its metabolites. Implications for neurodegenerative disease.
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.
Neurodegenerative Disease Research Centre, King's College, London, UK.
J P
JP
Spencer
A
A
Jenner
O I
OI
Aruoma
P J
PJ
Evans
H
H
Kaur
D T
DT
Dexter
P
P
Jenner
A J
AJ
Lees
D C
DC
Marsden
B
B
Halliwell
D001923:Brain Chemistry; D002384:Catalysis; D003300:Copper / Q000032:analysis / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004298:Dopamine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide; D007501:Iron / Q000032:analysis / Q000633:toxicity; D007980:Levodopa / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D014443:Tyrosine; D007980:Levodopa; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron; C008404:3-methoxytyrosine; D004298:Dopamine