Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen

Suzukawa, Andréia Akemi; Vieira, Antônio Wilson; Winnischofer, Sheila Maria Brochado; Scalfo, Alexsandra Cristina; Mascio, Paolo Di; Ferreira, Ana Maria da Costa; Ravanat, Jean‐Luc; Martins, Daniela de Luna; Rocha, Maria Eliane Merlin; Martinez, Gláucia Regina

doi:10.1016/j.freeradbiomed.2012.02.039

Cited by 37 publications

(22 citation statements)

References 86 publications

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“…Melanin is an important regulator of the balance of reactive oxygen species in melanocytes that could alter response of melanocytes to arsenic and UVR when compared to keratinocytes (Cunha et al, 2012; Jenkins and Grossman, 2013; Suzukawa et al, 2012). In this study, we investigate similarities and differences between purported mechanisms underlying arsenic and UVR-induced DNA damage in these two important target cells within the skin.…”

Section: Introductionmentioning

confidence: 99%

Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

2014

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The rise of melanoma incidence in the United States is a growing public health concern. A limited number of epidemiology studies suggest an association between arsenic levels and melanoma risk. Arsenic acts as a co-carcinogen with ultraviolet radiation (UVR) for the development of squamous cell carcinoma and proposed mechanisms include generation of oxidative stress by arsenic and UVR and inhibition of UVR-induced DNA repair by arsenic. In this study, we investigate similarities and differences in response to arsenic and UVR in keratinocytes and melanocytes. Normal melanocytes are markedly more resistant to UVR-induced cytotoxicity than normal keratinocytes, but both cell types are equally sensitive to arsenite. Melanocytes were more resistant to arsenite and UVR stimulation of superoxide production than keratinocytes, but the concentration of arsenite necessary to inhibit the activity of the DNA repair protein poly(ADP-ribose)polymerase and enhance retention of UVR-induced DNA damage was essentially equivalent in both cell types. These findings suggest that although melanocytes are less sensitive than keratinocytes to initial UVR-mediated DNA damage, both of these important target cells in the skin share a mechanism related to arsenic inhibition of DNA repair. These findings suggest that concurrent chronic arsenic exposure could promote retention of unrepaired DNA damage in melanocytes and act as a co-carcinogen in melanoma.

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Section: Introductionmentioning

confidence: 99%

Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

2014

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“…In summary, electron and proton radiation exposure both increase epidermal pigmentation and pigment incontinence in an acute manner as evidenced by changes in radiation-induced melanin trafficking. The important question of whether melanin production protects against radiation-induced DNA damage is debateable [25, 26]. …”

Section: Discussionmentioning

confidence: 99%

Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model

Sanzari

Diffenderfer

Hagan

et al. 2015

Life Sciences in Space Research

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The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the dermis upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed.

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“…Suzukawa found that melanins were found to bind to the minor grooves of DNA, guaranteeing close proximity to DNA and potentially causing the observed high levels of strand breaks. Moreover, they also found that after melanins interact with 1O2, they exhibit a lower ability to induce DNA breakage (Suzukawa, Vieira et al 2012). On the other hand, PDT shows its effect on melanoma cells by inducing photo-oxidative stress and cytotoxicity, where general response of cells is to upregulate their endogenous antioxidant systems, which in return neutralizes the efficacy of PDT treatment.…”

Section: Melanoma Resistance To Pdtmentioning

confidence: 99%

Melanoma resistance to photodynamic therapy: new insights

Huang

Vecchio²,

Avci³

et al. 2013

Biological Chemistry

107

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Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor.

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Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen

Cited by 37 publications

References 86 publications

Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

Melanocytes and keratinocytes have distinct and shared responses to ultraviolet radiation and arsenic

Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model

Melanoma resistance to photodynamic therapy: new insights

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