For Melanoma Etiology and Pathogenesis

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The adverse results of the ^-carotene and lung cancer prevention trials in which this nutrient (although at pharmacologic doses) led to more, rather than fewer, lung cancers in heavy smokers (Omenn et al. 1994) led me to reconsider the role of antioxidants in carcinogenesis, especially in melanoma genesis. One of the unique features of melanocytes is that they produce the unique differentiation product melanin whose major function has always been presumed to be protection against UVR. There are several unique features about melanin and its synthesis that merit comment:

• Hydrogen peroxide is generated and consumed during the synthesis of melanin.

• Melanin synthesis occurs in a complex and poorly understood complex organelle, the melanosome, which has many lysosomal properties.

• Melanin functions as an antioxidant in normal melanocytes.

For some time, it has been recognized that abnormalities of melanin synthesis lead to a range of benign pigmentary diseases. There is also available considerable descriptive data that has suggested melanosomes are abnormal in melanoma cells and became progressively deranged during the pathogenic process (Rhodes et al. 1988). However, the functional consequences of these abnormalities for transformation have been largely ignored.

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