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The effect of melanin content on UVA-induced DNA damage in melanocytes

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Abstract:
The UV portion of sunlight incident on human skin is composed of 95% long wavelength UVA, which can deeply penetrate to the skin’s basal layer to reach melanin-producing melanocytes and induce a pigmentation response. This natural defense mechanism protects skin cells from oxidative DNA damage such as double strand breaks (DSBs) caused by UVA-generated reactive oxygen species (ROS). The photoprotective brown-black eumelanin pigment synthesized in melanocytes absorbs UV wavelengths and prevents UV-induced DNA damage, while the photo-unstable yellow-red pheomelanin pigment has been shown to contribute to cellular ROS levels. Previously, our lab showed that these ROS could also act as signaling molecules involved in a UVA-activated Gaq/11 coupled pathway to trigger an increase in melanin synthesis and prevent further oxidative DNA damage. Here, we explore the complex role of melanin on UVA-induced ROS as both signaling molecules in early melanogenesis and a source of oxidative DNA damage. Via western blot analysis, we assessed levels of phosphorylated Histone H2AX (γH2AX), a DSB marker, in immortalized human epidermal melanocytes with differing eumelanin and pheomelanin amounts immediately after exposure to a physiological dose of UVA. Our results indicated higher levels of γH2AX in cells with low melanin compared to cells with high melanin, suggesting that UVA induces greater oxidative DNA damage in cells with less melanin and thus higher ROS levels. This finding is critical in understanding the balance between ROS involved in melanogenic signaling vs. damage-inducing high cellular ROS levels that accumulate in less pigmented cells exposed to UVA. The mechanisms of UV-induced DNA damage in populations with varying skin pigmentation phenotypes are key to understand and prevent resulting Inflammation, skin photoaging, and highly lethal skin cancers like melanoma.

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Citation

Alexandra Trouilloud, "The effect of melanin content on UVA-induced DNA damage in melanocytes" (2021). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/j6nj-yx05

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  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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