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Melanin: Our Natural Shade

Researchers are at work on a cream that would confer the beneficial effects of a tan yet shield us from the risks of the sun’s dangerous ultraviolet rays.

By Cathryn Delude // Winter 2011

The pigment melanin, whose production is spurred by tanning, helps protect skin from the cancer-causing effects of ultraviolet radiation by spreading over the nuclei of superficial skin cells, thus shielding the DNA below. But tanning—particularly for fair-skinned Caucasians, who do not brown easily—requires significant UV exposure.

David E. Fisher, director of the melanoma program at Massachusetts General Hospital Cancer Center and the hospital’s chief of dermatology, is looking for a way around this apparent catch-22.

To conduct his research, Fisher used biologically engineered red-haired, fair-skinned mice whose bodies could generate pigmented skin cells called melanocytes. After repeated applications of a special topical cream, these ginger-furred, light-skinned creatures became progressively more bronze, and their sunless tans protected them from skin cancer when they were exposed to UV light.

The cream contained compounds acting on molecules that Fisher’s research group had found to be involved in tanning. One compound, forskolin, stimulates a chemical messenger called cyclic AMP, which triggers melanin production in melanocytes, obviating the need for sunlight to trigger that production. The second compound, rolipram, deactivates an enzyme called PDE4D3, which degrades cyclic AMP and thus curtails tanning. By disabling this brake, the melanocytes keep churning out melanin.

The tanning strategy provides a “proof of principle” for true sunless tanning, but better drugs must be identified, with the capacity to penetrate humans’ thicker skin. The approach will also need further testing to ensure that it’s safe for long-term, repetitive use. “This strategy might prevent skin cancer in two ways,” Fisher says. “The tan it produces would directly block the UV radiation that causes skin cancer, and it would also give people an alternative way to tan without sunbathing or indoor tanning.”


Melanoma: Saving Our Skin

melanoma thumb

Melanoma, almost impossible to treat after it metastasizes, appears vulnerable to two new approaches that could someday be combined.

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