Ultraviolet B but not Ultraviolet A Radiation Initiates Melanoma

Abstract

Cutaneous malignant melanoma is one of the fastest increasing cancers with an incidence that has more than doubled in the last 25 years. Sunlight exposure is strongly implicated in the etiology of cutaneous malignant melanoma and the UV portion of the sunlight spectrum is considered responsible. Data are, however, conflicting on the roles of ultraviolet B [UVB; 280 -320 nanometers (nm)] and ultraviolet A (UVA; 320 -400 nm), which differ in their ability to initiate DNA damage, cell signaling pathways and immune alterations. To address this issue, we have used specialized optical sources, emitting isolated or combined UVB or UVA wavebands or solar simulating radiation, together with our hepatocyte growth factor/scatter factor-transgenic mouse model of UV-induced melanoma that uniquely recapitulates human disease. Only UVB-containing sources initiated melanoma. These were the isolated UVB waveband (>96% 280 -320 nm), the unfiltered F40 sunlamp (250 -800 nm) and the solar simulator (290 -800 nm). Kaplan-Meier survival analysis indicated that the isolated UVB waveband was more effective in initiating melanoma than either the F40 sunlamp or the solar simulator (modified log rank P < 0.02). The latter two sources showed similar melanoma effectiveness (P ‫؍‬ 0.38). In contrast, transgenic mice irradiated with either the isolated UVA waveband (>99.9% 320 -400 nm, 150 kJ/m 2 ), or an F40 sunlamp filtered to remove > 96% of the UVB, responded like unirradiated control animals. We conclude that, within the constraints of this animal model, UVB is responsible for the induction of mammalian cutaneous malignant melanoma whereas UVA is ineffective even at doses considered physiologically relevant. This finding may have major implications with respect both to risk assessment from exposure to solar and artificial UVB, and to development of effective protection strategies against melanoma induction by UVB. Moreover, these differences in wavelength effectiveness can now be exploited to identify UV pathways relevant to melanomagenesis.

Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets

“…Ultraviolet B (UVB) is a well-known major risk factor for the development of acute inflammation as well as non-melanoma skin cancer in epidermis (De Fabo et al, 2004;Ramos et al, 2004). Accumulating data indicate that UVB exerts its detrimental effect mainly through the induction of direct DNA damage or the production of reactive oxygen species (ROS) (de Gruijl, 2002;Kulms et al, 2002;Heck et al, 2003).…”

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

“…Studies in mammalian models, including the South American opossum (Monodelphis domestica) and several genetically modified mouse models, demonstrate that UVA does not induce melanomas (5)(6)(7). In contrast, evidence from all of these models, including Xiphophorus, supports a role for UVB in the etiology of melanoma.…”

Ultraviolet Light as a Modulator of Melanoma Development

“…Hence epidemiological data is somewhat supportive of the view that the full UVR spectrum may be carcinogenic in melanoma. It should be noted that at any point on the earth it is difficult to precisely predict the UVA/UVB ratio in sunlight as it can greatly vary with time of day, altitude, latitude and climate factors (De Fabo et al, 2004).…”

“…Despite it being a somewhat specialized system, there is much we can learn using the neonatal UVR about how UVR results in melanocyte transformation. For instance using the Mt-Hgf model (with overexpression hepatocyte growth factor throughout the skin) it has been shown that UVB, and not UVA, induces melanoma (de Fabo et al, 2004), and that use of sunscreen can attenuate its development (Klug et al, 2010). The skin of hairless mice contains some epidermal melanocytes, hence the animals represent a murine system amenable to chronic UVR exposures.…”