CANCER
September 27, 2006

Preventing Skin Cancer with — a Tan

A recently released study has produced an improved understanding of the process of skin tanning, a breakthrough that may lead to a new way of protecting fair-skinned people from skin cancer.

The study 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 — rather than burn — are far less likely to develop skin cancer than fair-skinned individuals, this 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, M.D., Ph.D., director of the Melanoma Program at Dana-Farber. 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% 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 long, dark winters. As human populations have scattered throughout the globe, increasing numbers of fair-skinned people have come to live in sunny climes and 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. Wehn these 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 sunburns.

"These animals couldn't tan," Fisher remarks. "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 study, published in the September 21 2006 issue of Nature also suggested that the traditional theory of the biology of tanning was wrong. In a series of experiments, Fisher's team developed a new model of how tanning occurs.

Fisher and his associates treated the skin of red-haired, fair-skinned mice with a compound containing a substance called forskolin that caused the mice to turn dark, proving that melanocytes in redheads aren't inherently unable to make pigment if appropriately stimulated.

Further experiments showed that not only can red-haired mice be given tans without exposing them to UV light, but this sunless tanning process is virtually indistinguishable from that in dark-haired mice that tan naturally.

They also showed that tans acquired through the forskolin treatment conferred significant protection against skin cancer caused by exposure to UV light.

"These studies suggest that a drug-induced 'rescue' of the tanning mechanism may correspondingly rescue at least some aspect of skin cancer protection," Fisher observes. "Such sunless tanning may also dissuade sun-seeking behaviors, which undoubtedly contribute significantly to high skin cancer incidence."

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