5-S-CYSTEINYLDOPA, A DIFFUSIBLE PRODUCT OF MELANOCYTE ACTIVITY, IS ANEFFICIENT INHIBITOR OF HYDROXYLATION OXIDATION REACTIONS INDUCED BY THE FENTON SYSTEM/

Interest in 5-S-cysteinyldopa (5-S-CD), a major excretion product of n ormal and malignant melanocytes, has traditionally concentrated on its significance as a biosynthetic precursor of pheomelanins, the charact eristic pigments of red hair, and as a specific biochemical marker for monitoring melanoma progression. The present study shows that 5-S-CD is a potent inhibitor of hydroxylation/oxidation reactions mediated by hydrogen peroxide and the Fe2+/EDTA complex under both aerobic and an aerobic conditions. The inhibitory effect of 5-S-CD, as determined by the deoxyribose and salicylic acid assays in phosphate buffer (pH 7.3) , is much stronger than that of dopa, acetylsalicylic acid and mannito l, increases with increasing ligand-to-metal ratio, and is inversely p roportional to the concentration of EDTA present in the Fenton system. Spectrophotometric evidence and competition experiments indicate that 5-S-CD forms a chelate complex with ferric ions (lambda(max) = 500 nm at pH 7.3), which may account for both an altered production of hydro xyl radicals by the Fenton reagent and a site-specific localization of oxidative damage on the chelate complex itself.