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Lotion gives mice tan, may be cancer shield

Melanin boosted without the sun

A lotion that tans the skin without exposure to sunlight could provide a novel way to prevent skin cancer, Boston scientists announced yesterday.

The research, done with mice, found that a lotion can prompt skin cells to make melanin, the darkening pigment that protects the skin from harmful ultraviolet radiation. After the lotion was applied for several days, the mice developed a light tan. After several weeks, the normally red- furred, fair-skinned mice were nearly black, according to Dr. David E. Fisher , who led the research at the Dana-Farber Cancer Institute and Children's Hospital Boston.

These dark tans provided some protection against a common kind of skin cancer and may protect against others, according to test results presented in today's issue of the journal Nature. The discovery is not ready for humans, Fisher cautioned.

Other scientists said the work provides a surprising new understanding of the biology behind the prized bronze-skinned look. Even fair-skinned people, who are more prone to develop skin cancer and less able to tan in the sun, have a deep reservoir of tanning ability that can be readily tapped, the discovery suggests.

``The principles that are shown in this study are quite startling and could have major ramifications," said Meenhard Herlyn , a skin cancer researcher who was not involved in the study and who works at Wistar Institute , an independent research institution in Philadelphia. ``Maybe in the future we can say, `You don't need to damage your skin; you can tan it in other ways.' "

About a million Americans every year are diagnosed with skin cancer, and exposure to the sun is thought to be an important cause. Most are successfully treated, but almost 8,000 Americans die annually from melanoma, a rare but highly lethal type of skin cancer.

The compound the scientists used to trigger the tanning is forskolin , which is sold as an herbal supplement derived from the root of a plant in India. Unlike tanning products sold today that dye the skin, the cream creates a real tan, with the color coming from the body's own cells.

Fisher said people should not try using the substance on their skin because it has not been carefully studied for toxicity as a skin cream. His lab is currently testing a number of other compounds that act on the same biological trigger as forskolin, with the hope that one of them will turn out to be a safe way to create a tan without the risks of bright sunlight or the tanning booth.

Fisher is cofounder of a Cambridge-based company, Magen Biosciences, that focuses on skin disorders and has licensed the right to use the technology from Dana-Farber. Magen is the Hebrew word for shield, he said.

The team, which also included researchers from Kentucky and Japan, made the discovery while exploring the genetics of tanning. It was thought that ultraviolet light triggered a type of skin cell called a melanocyte to produce a dark pigment, Fisher said. But the team found instead that a hormone, given off by other skin cells when they are exposed to the light, signals melanocytes to produce the pigment.

The hormone acts like a key fitting into a keyhole on the surface of the melanocyte. When the key slides in, the cell starts up the production of melanin. In fair-skinned people, the keyhole is misshapen, making it hard for the hormone to fit in and thus reducing production of the dark melanin. (This is thought to be a cellular adaptation to life in northern latitudes, where pigment interferes with the sun-driven production of Vitamin D.)

The team also found they could bypass the keyhole, essentially hot-wiring the cells to make melanin, by using forskolin-containing lotion. The tan was even and appeared normal, Fisher said, and it faded like any other tan after the researchers stopped applying the lotion.

They tried forskolin because they knew it would stimulate the production of a chemical called cAMP, which is known to be involved in producing tanning as well as many other cellular processes. There are drugs already available , designed to treat other conditions, that work because of this same chemical, Fisher said. It might be possible, he said, to adapt one of these drugs to be used as a skin cream.

Before any drug could be used as a tanning cream, it would have to go through extensive testing. One potential worry is that manipulating levels of cAMP might cause other, damaging changes, according to Dr. Boris Bastian , a melanoma scientist at the University of California, San Francisco. Humans also have thicker skin than mice, which might resist a skin cream, Fisher said.

The Boston team demonstrated that the tans are protective in mice. They began by breeding 18 mice with fair skin and a genetic change that makes them particularly prone to UV-induced skin cancers, including squamous cell cancer. Half of the mice were treated with the lotion for four weeks, producing a dark tan. All 18 mice were then exposed to daily sessions of UV light equivalent to 1 to 2 hours of midday Florida summer sun, according to the Nature paper.

The skin of the nine unprotected mice showed reddening, scarring, and thickening -- damage that can lead to skin cancer. In the nine tanned mice, such damage was ``significantly prevented," according to the paper. In addition, there were 11 tumors in the unprotected mice, and six in the tanned ones. Two of the nine unprotected mice had multiple tumors; none of the tanned ones did.

The researchers cautioned that the findings must be replicated with larger numbers of animals, and that the study didn't provide direct evidence that the lotion protects against melanoma.

Dana-Farber would not provide a photo of the mice for use by the news media, and a representative refused to provide a reason. Some scientists who work with animals worry about antagonizing animal-rights activists.

Gareth Cook can be reached at cook@globe.com.  

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