Abstract:Controversy continues both as to which wavelengths of sunlight cause melanoma and the mechanisms by which these different wavelengths act. Direct absorption of UVB by DNA is central in albino animal models, but melanin-pigmented models have shown major contributions by wavelengths longer than UVB that are thought to be mediated by photosensitized oxidant production. The only model for which the action spectrum of melanoma causation is known is a genetically melanoma-susceptible specific cross of Xiphophorus fi… Show more
“…Given our data, the action spectrum for melanoma does not correlate with the action spectrum for melanin radicals in Xiphophorus adult and neonatal fish (18). Hence, UVA-induced melanin radicals do not appear to be involved in melanomagenesis in this animal model.…”
Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning
confidence: 56%
“…Hence, there is no significant difference in the amount of melanin radicals produced by UVA and UVB at comparable doses. Given the quantitative similarity in the melanin radicals induced by UVA and UVB (18) and the relative inefficiency of ROS induction by UVB (23,24), we suggest that free radicals are not significantly involved in UVB-induced melanoma in the fish model. If ROS do not induce melanomas, it follows that the direct DNA damage associated with UVB plays a major role in the initiation of melanomas.…”
Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning
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...
“…Given our data, the action spectrum for melanoma does not correlate with the action spectrum for melanin radicals in Xiphophorus adult and neonatal fish (18). Hence, UVA-induced melanin radicals do not appear to be involved in melanomagenesis in this animal model.…”
Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning
confidence: 56%
“…Hence, there is no significant difference in the amount of melanin radicals produced by UVA and UVB at comparable doses. Given the quantitative similarity in the melanin radicals induced by UVA and UVB (18) and the relative inefficiency of ROS induction by UVB (23,24), we suggest that free radicals are not significantly involved in UVB-induced melanoma in the fish model. If ROS do not induce melanomas, it follows that the direct DNA damage associated with UVB plays a major role in the initiation of melanomas.…”
Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning
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...
“…Thus the fish experiments are carried out in the dark, and activation (by light) of the photolyase reduces melanoma incidence to background levels. 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.…”
Section: Evidence Of Uva Causality In Melanomamentioning
confidence: 99%
“…One would expect that if melanin sensitization were an important mechanism, we would not see the huge increase in melanoma risk for patients with XP, unless they also lacked a defence against the melanin radicals.However there remains an anomaly that Africans with albinism (i.e. no melanin, or low levels), who practice poor sun protection, have been consistently shown to only very rarely develop melanoma (reviewed in Wood et al, 2006). In 164 such patients in Tanzania actinic keratoses were found in 100%, and SCC in 34%, of albino individuals over 30 years old, but no melanomas were found (Lookingbill et al, 1995).…”
Section: Evidence Of Uva Causality In Melanomamentioning
“…2 Although melanin absorbs UV radiation and acts as an antioxidant, it may oxidize at higher doses which leads to additional cell damage. 3 The clinical presentation of doxycycline induced phototoxicity may vary from a sunburn-like sensation to diffuse erythematous plaques on sun-exposed areas. 4,5 The rash generally resolves within 10-14 days after discontinuation of the drug.…”
Commonly used in clinical practice, doxycycline has been known to produce a cutaneous phototoxic reaction in combination with sunlight. Several mechanisms have been proposed to contribute to its pathogenesis such as UVA oxidation of cellular components, the formation of photoproducts, and altered melanogenesis. We describe a case of a phototoxic rash in a patient taking doxycycline 100 mg daily for the treatment of rosacea. We present several photos of the rash from erythema to desquamation several weeks later. The clinical presentation of a doxycycline-induced phototoxic rash varies from a sunburn like sensation to diffuse erythematous plaques on sun exposed areas. Treatment involves discontinuing the drug and providing symptomatic relief. Although sunscreen may prevent a doxycycline-induced phototoxic reaction, it is important to educate the patient to use a sunscreen with protection in the 340-400 nm range in which phototoxic reactions are thought to occur. As doxycycline-induced phototoxicity is poorly understood, it may be best to advise the patient to avoid sun exposure altogether while taking the drug.
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