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

Abstract

We examined the wavelength dependence of ultraviolet (UV) radiation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.ultraviolet B | DNA damage | cyclobutane dimer | reactive oxygen species | melanin I n the late 1980s Setlow and coworkers used genetic hybrids from interspecific crosses involving several species of the fish genus Xiphophorus to investigate the effects of UVR on the induction of cutaneous malignant melanoma (CMM) (1). These pioneering studies demonstrated that ultraviolet B (UVB) irradiation of backcross hybrids generated from a specific genetic crossing scheme induced melanomas at significant frequencies above spontaneous levels. These results were later confirmed, and the genetic basis of UVB-induced melanoma susceptibility in this cross was recognized to be the same as in the well-studied spontaneous Xiphophorus hybrid melanoma model (2). In 1993, Setlow used a different Xiphophorus interspecies cross (designated as Sp-couchianus; Fig. 1) to study the wavelength dependence of melanoma induction and reported that wavelengths in the ultraviolet A (UVA) and visible ranges were effective in inducing melanomas in first-generation backcross (BC 1 ) hybrids generated from this particular cross (3). An action spectrum for melanoma induction was proposed with maxima in the UVB (302/313 nm) and UVA (365 nm) ranges. Because UVA fluence is quantitatively much greater than UVB in sunlight incident to the earth's surface (∼10-fold), Setlow suggested that, on the basis of this action spectrum, UVA was more effective than UVB in causing melanomas in the human population (2, 4). This report had significant public health consequences; it suggested that the use of commercially available sunscreens that effectively blocked UVB but not UVA encouraged more lengthy recreational sunlight exposure and thereby increased the exposure to UVA and its associated risks. Over the past 20 years, these data have become central to the debate on the role of UVA in melanoma and the risks associated with recreational and artificial exposures to UVA wavelengths.Debate over the action spectrum for melanoma has only intensified because subsequent r...

Photosensitised pyrimidine dimerisation in DNA

“…Thus, studies performed on animals (opossum, 4 fish, 5 mice 6 ) suggest that it provokes the formation of papillomas, squamous cell 35 carcinomas (SCC) and melanomas; however, the role played by UVA-mediated oxidative damage to DNA in melanoma induction, using xiphophorus fishes as model, has been recently questioned. 5,7 While UVB is efficiently absorbed by the nucleobases, 40 causing direct photoreactions of DNA, UVA-induced damage is commonly the result of photosensitisation. Thus, modifications in DNA may occur after light absorption by endogenous or exogenous chromophores present in drugs, cosmetic agents, metabolites, etc.…”

18-årsgrensen for solariebruk skal håndheves

“…Studies in these fish however showed that visible and UVA radiation, as well as UVB (Setlow et al, 1993) induced lesions, which raised concern that UVA might be causal for human melanoma as well or instead of UVB. However this could not be confirmed in later experiments (Mitchell et al, 2010). A mammalian opossum model also developed melanoma-like lesions after broadband UVA exposure but with low potency compared to broad-band UVB (Robinson et al, 2000).…”

Ultraviolet Light as a Modulator of Melanoma Development

“…Recently Timmins and colleagues used electron paramagnetic resonance assays to show that the action spectrum for melanoma and melanin radical production overlap (Wood et al, 2006), further evidence for melanin radical causation. However the notion that UVA is more effective than UVB in inducing melanoma in fish has been questioned by Mitchell et al, (2010), after similar experiments using apparently the same strain of fish. This conflicting result from the original study (Setlow et al, 1989) may be largely explained by the fact that latest study used more animals to make the results more statistically significant, and followed the fish for a longer time, allowing for later age of onset of some melanomas.…”