Radicals and melanomas

Abstract

The synthesis of melanin involves the oxidation of phenolic substrates by the enzyme tyrosinase. In vertebrates tyrosinase is present only in specialized cells (melanocytes), where it catalyses the oxidation of tyrosine and certain diphenolic intermediate products to quinones which polymerize to give rise to melanin. This specialized metabolic pathway provides a possible approach to the specific chemotherapy of malignant tumours of pigment cells (malignant melanoma). Certain analogues of tyrosine are oxidized by tyrosinase generating reactive orthoquinones with cytotoxic potential. One such analogue, 4-hydroxyanisole, has been investigated as a possible specific melanocytotoxic precursor. The parent compound inhibits DNA synthesis but exhibits little general toxicity, while the tyrosinase oxidation products are highly toxic to cells. The mechanism of this toxicity may involve semiquinone radicals. Encouraging initial results have been obtained from clinical pilot studies using intra-arterial infusion of hydroxyanisole in patients with localized recurrences of malignant melanoma.