OXIDATIVE DNA-DAMAGE IN THE PARKINSONIAN BRAIN - AN APPARENT SELECTIVE INCREASE IN 8-HYDROXYGUANINE LEVELS IN SUBSTANTIA-NIGRA

Oxidative damage has been implicated in the pathology of Parkinson's d isease (PD), e.g., rises in the level of the DNA damage product, 8-hyd roxy-2'-deoxyguanosine, have been reported. However, many other produc ts result from oxidative DNA damage, and the pattern of products can b e diagnostic of the oxidizing species. Gas chromatography/mass spectro metry was used to examine products of oxidation and deamination of all four DNA bases in control and PD brains. Products were detected in al l brain regions examined, both normal and PD. Analysis showed that lev els of 8-hydroxyguanine (8-OHG) tended to be elevated and levels of 2, 6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine) tended to be decreased in PD. The most striking difference was a rise in 8-OHG in P a substantia nigra (p = 0.0002); rises in other base oxidation/deamina tion products were not evident, showing that elevation in 8-OHG is unl ikely to be due to peroxynitrite (ONOO-) or hydroxyl radicals (OH.), o r to be a prooxidant effect of treatment with L-Dopa, However, some or ail of the rise in 8-OHG could be due to a change in 8-OHG/FAPy guani ne ratios rather than to an increase in total oxidative guanine damage .