Melanin precursors

Clonogenic survival of B16 melanoma cells measured after exposure to graded doses of 211 At-AMT for 45 minutes is represented in Figure 12, showing that this radiolabelled modified melanin precursor is exceptionally cytotoxic. The linear cell survival curve, without a shoulder in the low-dose region, is characterisitc for high-LET a radiation125. 

Pulse radiolysis investigation of oxidation of melanin precursors... 

An investigation of the oxidation of melanin precursors in the presence of azide radicals using pulse radiolysis has been reported (2J9. Thus, dopa and cysteinyldopa yielded first the unstable semiquinones that disproportionated to a quinone-quinol complex. The quinones decayed to more stable products dopaquinone produced dopachrome while cystei-nyldopa-quinones rearranged to benzothiazine isomers. 

Since the melanin precursors are known and since the mode of interactions to form the pigment is not unlimited, one might expect that the chemical reactivity pattern of melanin should reflect that of its precursors. The results of investigations suggest that this is indeed the case, and, thus, the long-held view of the chemical inertness of this material is being rapidly abandoned. 

Malignant melanocytes present defective melanosomes and tend to exhibit up-regulated melanogenesis. Melanogenuria (in the form of dark urine) is observed in some patients with widespread disease. End-product pigments, enzymes and melanin precursors or intermediates of the melanogenesis have therefore been measured in urine and blood from melanoma patients for more than 30 years. 

The deoxygenation of a polyphenolic melanin precursor can be effected biologically and the role of NADPH in this has been studied (ref.58)... 

Gonzaulez A M, Benintez L, Soto T, et al. (1997). A rapid bioassay to detect mycotoxins using a melanin precursor overproducer mutant of the ciliate Tetrahymena thermophila. Cell Biol. Ini. 21 213-216. 

Melanins, although superficially inert, possess some biologically significant physicochemical properties by acting as radical scavengers, ion-exchangers, metal-binder, etc. (55). Extensive studies of the chemical reactivities of melanin and putative melanin precursors have led researchers into many areas of scientific research the results of which have been reviewed (55, 70, 92, 123, 184, 211, 259, 264, 265). 

It appears from the previous discussion that melanogenesis in vivo or in vitro is regulated by various factors. Hence, to study the dynamics of melanin formation (monooxygenase reaction, i.e. constructive metabolism) and breakdown (dioxygenase reaction, i.e. catabolism of melanin precursors), a non-enzymatic melanin synthesis from tyrosine and tryptophan, respectively, was devised by Roy et al. (227), using a prototype of a monooxygenase reaction, i.e. the Udenfriend reaction (Fe+ /EDTA/ ascorbic acid) (272). 

All these results show the close resemhlance of tryptophan to tyrosine and dopa, with respect to their role as melanin precursors as well as positive regulators of tyrosinase. 

Lambert C, Chacon JN, Chedekel MR, Land EJ, Riley PA, Thompson A, Truscott G (1989) A Pulse Radiolysis Investigation of the Oxidation of Indolic Melanin Precursors Evidence for Indolequinones and Subsequent Intermediates. Biochim Biophys Acta 993 12... 

The reaction of peroxynitrite with the melanin precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA) produces polymeric products. The reaction proceeds through unstable intermediates including dimers and trimers of DHICA in addition to indole-5,6-quinone-2-carboxylic acid thus peroxynitrite, which nitrates phenolic compounds. 

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