: D'Orazio et al., Nature 443, 340 (21 September 2006)

Tan-tastic
Mice with chemically induced tans are interspersed between their more pallid brethren.

Better Tanning Through Chemistry

Redheads rejoice! Scientists have found a way to chemically stimulate the tanning process without sun exposure. The approach not only offers the pallid that elusive bronze tan but could also one day reduce the risk of melanoma--a cancer that kills 6000 mostly fair-skinned people a year in the United States.

The prevailing theory of how skin tans posits that ultraviolet (UV) light damages the DNA of cells called melanocytes, causing an overproduction of the darkening pigment melanin. But a report in tomorrow's issue of Nature reveals that UV light actually harms keratinocytes, the most plentiful cell type in the skin. Once damaged, the cells release melanocyte-stimulating hormone (MSH), a compound that binds to a receptor on melanocytes called MC1R, which in turn stimulates the production of melanin and darkens the skin.

The finding explains why many people with fair skin and red hair can't tan, says lead study author David Fisher, a medical oncologist at the Dana-Farber Cancer Institute in Boston and Children's Hospital Boston. According to a 1995 study, these people tend to have a mutation in their MC1R gene that prevents MSH from binding to the receptor and signaling melanin release.

To see whether there's any hope for the tanless, Fisher's team applied a topical cream to mice genetically altered to have fair skin and a dysfunctional MC1R receptor. The cream contains a plant-derived chemical called forskolin, which bypasses the receptor, directly activating a series of reactions normally stimulated by MC1R. In just a few weeks, the fair-skinned mice turned dark brown. Tests revealed that the melanin in the darkened mice was chemically identical to melanin produced in normal mice. What's more, the newly bronzed rodents gained benefits usually attributed to darker-skinned people: When exposed repetitively to UV light, they were far less likely to develop skin cancer than were mice that received no forskolin.

But don't rush out and start rubbing yourself with plant extract. Forskolin probably has too many side effects for human use, says Fisher. However, he notes, several currently available drugs stimulate the same pathways as forskolin, including some prescribed for asthma. "We don't know yet whether [these results] will hold up in humans, but there is enough circumstantial evidence to suggest that that would be the case," says Meenhard Herlyn, a tumor biologist at the Wistar Institute in Philadelphia, Pennsylvania. Work with human skin has already begun, says Fisher, who hopes to report preliminary findings in about a year.

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