No increased chromosomal damage in L-DOPA-treated patients with Parkinson's disease: a pilot study

Parkinson's disease (PD) is a neurodegenerative movement disorder affecting about 2% of the human population in old age. l-3,4-Dihydroxyphenylalanine (l-DOPA) in combination with a peripheral aromatic amino acid decarboxylase inhibition has been the most frequently prescribed drug for alleviating symptoms of PD, but a potential contribution of l-DOPA therapy to further neurodegeneration via oxidative stress is still debated. We report that the specific oxidative stress biomarker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) level in peripheral blood lymphocyte DNA was elevated to 8.1 +/- A 1.7 8-oxodG/10(6)dG in 17 chronically l-DOPA-treated PD patients, compared to 4.6 +/- A 1.2 8-oxodG/10(6)dG in 12 controls. However, the total antioxidative capacity of plasma was increased to 1113 +/- A 237 mu M in the PD patients compared to 941 +/- A 254 mu M in controls. The frequency of micronuclei, a subgroup of chromosomal aberrations, in peripheral blood lymphocytes was not elevated compared to healthy age-matched individuals. In vitro, in a cell-free assay, dopamine and its precursor l-DOPA exhibited antioxidative capacity. On the other hand, the 8-oxodG concentration in cultured PC 12 cells was enhanced after dopamine treatment. This elevation may be below a threshold for manifestation as chromosomal damage.