Antioxidant Defense and UV-Induced Melanogenesis: Implications for Melanoma Prevention

Ultraviolet radiation (UVR) has been implicated as a major environmental factor in the pathogenesis of photoaging and skin cancers including melanoma. Hypermelanosis induced by UVR has been previously suggested to associate with melanomageneis, although the role of UVR in the development of melanoma is complicated since melanogenesis may depend on several factors such as skin type, genetic influence, the extent of sun exposure (e.g., intensity, timing and duration of UVR) and types of moles representing disturbed melanin synthesis (Parvel et al., 2004; Rass & Reichrath, 2008; Tran et al., 2008). Melanin has been well recognized for its photoprotective properties, although melanogenic intermediates can be phototoxic and UVR-dependent elevated melanogenesis could thus be biologically harmful, genotoxic and contributed to melanoma initiation, especially in lightly pigmented individuals (Brenner & Hearing, 2008; Smit et al., 2008; Takeuchi et al., 2004; Yamaguchi et al., 2006). The desire to have fair or tanned skin depends on different cultures. The use of whitening agents has been growing in the Eastern culture, whereas having tanned skin is favorable and attractive in the Western culture that makes artificial tanning products become increasingly popular. Various factors including endocrine and environmental factors, in particular UVR, affect melanogenesis, mainly regulated by tyrosinase in melanocytes and/ or melanoma cells, in response to physiological and pathological changes (H.Y. Park et al., 2009; Slominski et al., 2004). This chapter focuses on the role of UV-induced oxidative stress in association with melanogenesis, which can be modulated by antioxidant defenses. Several studies have supported the relationship between UVR-mediated melanogenesis and oxidative stress, which takes place when there is increased production of reactive oxygen species (ROS) and/ or reactive nitrogen species (RNS) as well as antioxidant network impairment (Baldea et al., 2009; H.T. Wang et al., 2010). Therefore, improving antioxidant defense capacity to cope with oxidative insults may be beneficial in attenuation of abnormal production of melanin that could have a biological significance for the skin in protecting against photodamage. Whereas hyperpigmentation mediated by UV irradiation could reflect a sign of defensive response of the skin to stress, alteration in melanin synthesis may be implicated in skin damage and probably melanomagenesis, particularly in individuals with fair skin. Therefore, understanding the mechanisms by which antioxidants may modulate UVR-