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Using a mouse model of "redheads," David E. Fisher of the Dana-Farber Cancer Institute, Boston, and his coworkers have shown that the natural skin-tanning pathway can be jump-started by topical application of the plant-derived natural product forskolin, shown (Nature 2006, 443, 340). Tanning is a protective response of the skin to ultraviolet radiation, and the pigment pathway resulting in a tan is often defective in people with fair hair and skin, such as redheads. The researchers found that mice genetically engineered to lack the melanocortin 1 receptor, which is normally located on the surface of pigment cells, produced no pigment in response to UV light. But the mice progressively became so dark in response to forskolin that they looked like naturally dark mice. The pigment produced in this manner acts just like naturally produced pigment, collecting in umbrella-like arcs over the nuclei of skin cells known as keratinocytes. The forskolin-treated mice were thus protected against potential skin damage or cancer that can be caused by UV exposure. Studies are currently under way to identify drugs that may have similar activity in human skin, Fisher says.
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