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Intense oxidative DNA damage promoted by l ‐DOPA and its metabolites implications for neurodegenerative disease
Author(s) -
Spencer Jeremy P.E.,
Jenner Andrew,
Aruoma Okezie I.,
Evans Patricia J.,
Kaur Harparkash,
Dexter David T.,
Jenner Peter,
Lees Andrew J.,
Marsden David C.,
Halliwell Barry
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01056-0
Subject(s) - dna damage , oxidative phosphorylation , chemistry , dna , neurotoxicity , oxidative damage , dopamine , amyotrophic lateral sclerosis , oxidative stress , biochemistry , programmed cell death , dna oxidation , mutation , disease , biology , toxicity , medicine , apoptosis , gene , endocrinology , organic chemistry
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 2 O 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.