New insight into skin-tanning process suggests novel way of preventing skin cancer

Though synthetic images and contrived looks help to shape our ideas of what’s attractive and what’s passe, we suspect the suntanned look triggers recognition of a healthy, robust outdoorsy person and no matter what shape the Ozone Layer is in, the bronzed look is still likely to be fashionable for a long time yet. Which makes the following great news for the sun worshippers of the world. Findings from a study led by researchers at Dana-Farber Cancer Institute and Children's Hospital in Boston have rewritten science's understanding of the process of skin tanning – an insight that has enabled them to develop a promising way of protecting fair-skinned people from skin cancer caused by exposure to sunlight.

The study, to be published by the journal Nature in its Sept. 21 issue, involved giving tans to specially engineered mice, not by exposing them to ultraviolet rays in sunlight (the usual route to a tan), but by applying a cream that switched on the tanning machinery in their skin cells. Because people who tan easily, or have naturally dark skin, are far less likely to develop skin cancer than fair-skinned individuals – who tend to get sunburns rather than tan – the findings suggests that medicinally-induced tans can protect at-risk individuals from the disease.

"The study involved using a small molecule to essentially mimic the process that occurs when skin cells are struck by ultraviolet light from the sun," says the study's senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston. While the compound used in the study has not yet been tested in humans, the results "demonstrate the principle that actual tanning can be 'rescued' by recognizing the normal pathway and the precise step where it is blocked in people who do not tan well," he remarks.

Melanoma is the fastest-increasing form of cancer in the world, accounting for 62,000 new cases in the United States every year and nearly 8,000 deaths, according to the American Cancer Society. It occurs when pigment-making skin cells called melanocytes begin dividing rampantly as a result of damage to their DNA. If melanoma tumors are detected and surgically removed before their cells spread to other parts of the body, patients have an almost 100 percent chance of surviving. The odds drop sharply, however, if treatment doesn't begin until the disease has spread, or metastasized.

One trigger for melanoma development appears to be ultraviolet (UV) light from the sun, which can damage the skin's DNA. For most of human history, fair-skinned people, who tan poorly, occupied regions with low sun exposure, such as Nordic areas with winter months of darkness. As human populations have scattered throughout the globe, increasing numbers of fair-skinned people have come to live in sunny climes, and melanoma and other skin cancer rates have shot up.

The new Dana-Farber report grew out of efforts by Fisher's laboratory to study melanoma in mice whose fair skin stemmed from the same genetic roots as fair-skinned people. The researchers succeeded in generating red-haired mice whose light skin contained melanocytes, but when the mice were subjected to low levels of UV radiation, they did not tan. Nor did they tan when the UV levels were raised slightly; but when they increased slightly more, the animals got skin sunburns.

"These animals couldn't tan," Fisher remarks, who is also a professor of pediatrics at Harvard Medical School. "We'd proven in a rigorous genetic system what people have known for hundreds of years: Redheads don't tan well."

This suggested that the mice were a good model for fair-skinned humans. It also led researchers to propose a new theory about how sun exposure triggers pigmentation in people who tan easily. If the researchers' theory was correct, it should be possible to induce dark pigmentation in fair-skinned mice with specific, targeted drugs.

The most common origin of red hair and pale skin in humans is found in a tiny pouch-like receptor, called MC1R, on the surface of melanocytes. When the hormone MSH — for Melanocyte Stimulating Hormone — drops into the pouch, it causes a surge in the melanocyte's production of the chemical cAMP. cAMP then stimulates melanocytes to turn on a large number of genes, causing a pigment called melanin to be produced. If cAMP levels are low, the melanocytes make red/blond melanin. If cAMP levels are high, they make brown/black melanin. The melanin is eventually discharged from melanocytes and taken up by keratinocytes. MC1R is shaped differently in red-haired people, so that MSH cannot stimulate it strongly. The result is that cAMP production stays at low levels. Less cAMP means less red/blond pigment production, which results in fair skin.

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