Commentary: Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure

Citation: Gajula RP and Gaddameedhi S (2015) Commentary: Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Front. Physiol. 6:276. Cutaneous malignant melanoma (CMM) is one of the most rapidly increasing cancers in the western world (Bowden, 2004). Frequency of its occurrence is closely associated with skin color and depends on geographical zone (Leiter and Garbe, 2008). Multiple epidemiological studies in humans (Whiteman et al., 2007) and experimental studies with mouse melanoma models suggest that sunburn during childhood confers the highest risk of melanoma development later in life (Noonan et al., 2001). Ultraviolet radiation (UVR) from sunlight that reaches earth is comprised of 90–99% UVA (320–400 nm) and 1–10% UVB (280–320 nm), as most UVB is absorbed by stratospheric ozone (Bowden, 2004). High energy UVB is strongly absorbed by epidermal genomic DNA resulting in direct DNA damage by generating two major photoproducts: cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4 PPs), both of which are mutagenic and carcinogenic in animal models as well as in humans (Bowden, 2004; Lima-Bessa and Menck, 2005). These photoproducts are solely repaired by the process of nucleotide excision repair (Sancar et al., 2004) and the loss of this repair system is strongly correlated with increased melanoma. This loss results from transformed melanocytes, while non-melanoma skin cancers originate from malignantly transformed keratinocytes (Kraemer, 1997; Bowden, 2004). Although it was established that melanin that is specifically synthesized within melanocytes protects against direct DNA damage by absorbing the energy from UVR (Sinha and Häder, 2002). Recent findings from two independent research groups suggest that melanin might contribute to additional DNA damage and might further lead to increased risk of skin cancers (Noonan et al., 2012; Premi et al., 2015). Using hepatocyte growth factor/scatter factor (HGF) transgenic mice with a controlled UVR delivering system on neonatal mice, Noonan et al., have unraveled interesting findings regarding UVA and UVB-induced melanomagenesis (Noonan et al., 2012). In their experiments, 3 day old C57BL/6-HGF (Black and melanin pigmented), C57BL/6-c-HGF tyrosinase mutant (Albino and no melanin pigment) transgenic mice were irradiated with both UVA and UVB, then with specific UVA or UVB at a biological dosage. The authors have found that UV induction of melanin contributes to melanomagenesis only by UVA and not by UVB radiation. This UVA-mediated melanoma development was associated with oxidative DNA damage in melanin containing black mice and not in albino mice from the same genetic background. However, …