(Pheo)Melanin Photosensitizes UVA-Induced DNA Damage in Cultured Human Melanocytes

Abstract

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by culturing at two different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the main precursor of melanin. In parallel, pheo- and total melanin contents of the cells were determined. Identical experiments were performed with two melanocyte cultures derived from a skin type I and a skin type VI individual. For the first time the correlation between UVA-induced genotoxicity and pheo-/total melanin content has been investigated. We observed that cultured in basic medium, the skin type VI melanocytes contained 10 times more total melanin and about seven times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine level in the culture medium resulted in an increase of both pheo- and total melanin levels in both melanocyte cultures; however, the melanin composition of skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI melanocytes remained the same. The skin type VI melanocytes cultured in basic medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per m2) toward UVA that is probably related to their high pheo- and total melanin content. Their UVA sensitivity, however, did not change after increasing their melanin content by culturing at high tyrosine concentration. In contrast, the skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da per kJ per m2) toward UVA when cultured in basic medium, but increasing their melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated cultured human melanocytes are photosensitized by their own synthesized chromophores, most likely pheomelanin and/or melanin intermediates.

What Controls Variation in Human Skin Color?

“…In Australia, the lifetime cumulative incidence of skin cancer approaches 50%, yet the oxymoronic “smart tanning” industry continues to grow, and there is controversy over the extent to which different types of melanin can influence susceptibility to ultraviolet (UV) radiation (Schmitz et al 1995; Wenczl et al 1998). At the other end of the spectrum, inadequate exposure to sunlight, leading to vitamin D deficiency and rickets, has been mostly cured by nutritional advances made in the early 1900s.…”

Associations between environmental factors and incidence of cutaneous melanoma. Review

“…3-hydroxypyridine derivatives comprising a wide range of skin biomolecules, such as enzymatic collagen cross-links, B6 vitamin, and likely advanced glycation end products in chronologically aged skin, constitute a novel class of UVA photosensitizers, capable of skin photooxidative damage [38]. Wenczl et al [39] demonstrated that UVA-irradiated cultured human melanocytes are photosensitized also by chromophores as pheomelanin and/or melanin intermediates. UVB natural chromophores may also exhibit similar phototoxic properties.…”

Mouse models of UV-induced melanoma: genetics, pathology, and clinical relevance

“…Human epidemiological data and in vitro experiments further support the role of pigment (particularly pheomelanin) in enhancing UVA-induced DNA damage. 74–77 Studies using mice with varying amounts of pheomelanin show that increased oxidative damage in melanocytes with high levels of pheomelanin can occur independent of UVR, indicating the need for further investigation of UVR and pigment. 6 The type of melanin may impact the complex interactions between UVA and pigment.…”