The cutaneous melanocyte as a target of environmental stressors: Molecular mechanisms and opportunities

Abstract

Pigmentation is regarded as a natural way to protect skin against harmful impact of UV from sunlight. In fact, prevalence of sunburn or skin cancer (carcinoma and melanoma) is lower in individuals with dark skin, suggesting that melanin is an efficient sunscreen. However, UV-induced melanoma generally originates from pigmented cells or pigmented skin areas (nevi) and in vitro or in vivo data have shown that melanin and/or its precursors could also be a source of photo-oxidative stress. Pigmentation behaves thus like a two-edged sword. Despite this adverse biological context, melanocytes generally persist a long time in skin probably because of specific abilities to repair DNA, to manage oxidative stress and to resist apoptosis. In addition to sunlight, melanocytes can also be targeted by specific chemicals whose toxicity is linked to the melanogenic pathway. For instance, activation of phase I metabolism through AhR pathway can stimulate pigmentation whereas biochemical transformation of some phenols by tyrosinase can trigger melanocyte death. In conclusion, due to its very peculiar physiology, the melanocyte is a unique and delicate cell type in epidermis. Since its alteration can give rise to melanoma, one of the most dangerous cancers, a specific protection is required to ensure pigment cell homeostasis.