Wenczl E, Van der Schans G P, Roza L, Kolb R M, Timmerman A J, Smit N P, Pavel S, Schothorst A A
Department of Dermatology, Kun Street Hospital, Budapest, Hungary.
J Invest Dermatol. 1998 Oct;111(4):678-82. doi: 10.1046/j.1523-1747.1998.00357.x.
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.
黑色素在人类皮肤细胞中是起到光保护作用还是光致敏作用，这一问题仍存在争议。为了评估黑色素在紫外线A（UVA）照射时的作用，我们检测了人类黑色素细胞中的DNA单链断裂（ssb）情况。这些黑色素细胞仅因在两种不同浓度的L - 酪氨酸（黑色素的主要前体）中培养而产生的色素量不同，分别为基础浓度（0.01 mM）或高浓度（0.2 mM）。同时，还测定了细胞中的褐黑素和总黑色素含量。我们使用来自I型皮肤个体和VI型皮肤个体的两种黑色素细胞培养物进行了相同的实验。首次研究了UVA诱导的遗传毒性与褐黑素/总黑色素含量之间的相关性。我们观察到，在基础培养基中培养时，VI型皮肤的黑色素细胞所含的总黑色素比I型皮肤的黑色素细胞多10倍，褐黑素多约7倍。培养基中酪氨酸水平的升高导致两种黑色素细胞培养物中的褐黑素和总黑色素水平均增加；然而，I型皮肤黑色素细胞的黑色素组成变得更倾向于产生褐黑素，而VI型皮肤黑色素细胞的黑色素组成保持不变。在基础培养基中培养的VI型皮肤黑色素细胞对UVA表现出非常高的敏感性（每10(10) Da每kJ每m2有1.18个ssb），这可能与其高含量的褐黑素和总黑色素有关。然而，在高酪氨酸浓度下培养增加其黑色素含量后，它们对UVA的敏感性并未改变。相比之下，I型皮肤黑色素细胞在基础培养基中培养时对UVA表现出低敏感性（每10(10) Da每kJ每m2有0.04个ssb），但增加其黑色素含量会导致其对UVA的敏感性增加3倍（每10(10) Da每kJ每m2有0.13个ssb）。这些结果表明，经UVA照射的培养人类黑色素细胞会被其自身合成的发色团（最有可能是褐黑素和/或黑色素中间体）光致敏。
