UV blocker: lotion yields protective tan in fair-skinned mice.

A lotion that stimulates production of the skin pigment melanin induces a deep tan in specially bred laboratory mice. Those mice have skin similar to that of red-headed, fair-skinned people, who are notoriously poor tanners.

The animals developed their tans without being exposed to the sun and its ultraviolet (UV) rays. Further tests showed that the additional melanin protected the mice against UV-induced DNA damage, sunburn, and skin cancer.

The active ingredient in the lotion is forskolin, an Asian plant extract that has been used to treat health problems. But scientific studies of the compound in the past few decades have shown no clear benefit, says study coauthor David E. Fisher, an oncologist at the Dana-Farber Cancer Institute and Children's Hospital in Boston. Nevertheless, past tests had shown that forskolin can rev up production of cyclic AMP, a molecule that's instrumental in producing melanin.

Normally, melanin manufacture requires several steps. When sunlight's UV rays hit the skin, cells release a signaling compound that binds to proteins on the surface of melanocytes, the cells that make melanin. This docking activates cyclic AMP production inside the melanocyte, which spurs the cell to make melanin and distribute it to nearby skin cells.

There, melanin forms an array of microscopic parasols over the skin cells' nuclei, shielding the DNA from ultraviolet rays. The melanin darkens the cell and reduces burn risk.

In the new study, Fisher and his team used mice that, like red-headed people, have surface proteins on their melanocytes that are poor docking stations for the signaling compound. That interrupts melanin production.

Mice coated with the forskolin lotion for 3 weeks made more melanin and became dramatically darker than mice getting a neutral lotion.

Untreated mice exposed to UV rays for 24 hours had more than 20 times as much DNA damage and sunburn as did mice that had been treated with forskolin. After 20 weeks of exposure to UV rays for an hour or so each day, untreated mice developed nearly twice as many skin tumors as did the treated mice, the scientists report in the Sept. 21 Nature.

The results show that "the reduced DNA damage has a [positive] biological consequence," says molecular biologist Richard A. Sturm of the University of Queensland in Brisbane, Australia. Increased melanin reduced death among skin cells.

Studies had previously established that people with dark skin are less likely to become sunburned or get skin cancer than fair-skinned people are. With the new work, Sturm says, Fisher and his team "display the tangible proof ... for a photo-protective role of melanin."

Sturm is cautious about the possibility of providing people with a forskolin-containing cream. He notes that cyclic AMP can stimulate cell growth, so increased amounts of that molecule might pose a cancer risk.

Fisher is cautious too. "I am far from certain [that such a cream] would have activity in human skin," he says. Still, the findings suggest that intervening in the melanin-production process has potential as a cancer preventive, he says.

"If [forskolin] turns out to be safe and acceptable for human use, it can only be helpful," says dermatologist Barbara A. Gilchrest of Boston University School of Medicine.