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Abstract
Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM). However, the UV-related pathogenetic mechanisms leading to CMM are far to be fully elucidated. In this paper we will focus on what we still don't fully know about the relationship between UVR and CMM. In particular, we will discuss: the action spectrum of human CMM, how different modalities of exposure (continuous/ intermittent; erythemal/ suberythemal) relate to different CMM variants, the preferential UVR induced DNA mutations observed in different CMM variants, the role of UV-related and UV-unrelated genetic damages in the same melanoma cells. Moreover, we will debate the importance of UVA induced oxidative and anaerobic damages to DNA and other cell structures and the role of melanins, of modulation of innate and acquired immunity, of vitamin D and of chronic exposure to phototoxic drugs and other xenobiotics. A better understanding of these issues will help developing more effective preventative strategies and new therapeutic approaches.
Highlights
It is widely accepted that ultraviolet light radiation (UVR) is the major—but not the only— risk factor for the development of cutaneous malignant melanoma (CMM) [1]
It is completely unclear why different modalities of UVR exposure induce different molecular damages in the same cell population [2] and why these different molecular damages lead to different clinical CMM variants
We emphasize how important it is to extrapolate in a very careful and critical manner the results of experimental studies about photo-genotoxicity made with cell cultures: during “in-vivo” UV exposure, while UVA has a deeper penetration, only a small fraction of the incident UVB radiation reaches the level of the dermal-epidermal junction of human skin, where melanocytes are located
Summary
Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM). The UV-related pathogenetic mechanisms leading to CMM are far to be fully elucidated. In this paper we will focus on what we still don’t fully know about the relationship between UVR and CMM. We will discuss: the action spectrum of human CMM, how different modalities of exposure (continuous/ intermittent; erythemal/ suberythemal) relate to different CMM variants, the preferential UVR induced DNA mutations observed in different CMM variants, the role of UV-related and UV-unrelated genetic damages in the same melanoma cells. We will debate the importance of UVA induced oxidative and anaerobic damages to DNA and other cell structures and the role of melanins, of modulation of innate and acquired immunity, of vitamin D and of chronic exposure to phototoxic drugs and other xenobiotics.
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