New findings in a study of the process of skin tanning reveal a promising way of protecting fair-skinned people from skin cancer caused by exposure to sunlight.

In a new research done on mice scientists have developed a cream that switched on the tanning machinery in the skin cells without exposing them to sun. This new understanding of the process of skin tanning enabled them to develop a promising way of protecting fair-skinned people from skin cancer caused by exposure to sunlight.

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 tans -- the findings suggests that medicinally-induced tans can protect at-risk individuals from the disease.

The study used a small molecule that essentially mimics the process that occurs when skin cells are struck by ultraviolet light from the sun. 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. Melanoma, the fastest-increasing form of cancer in the world, 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.

Red hair and pale skin humans do not tan easily because of a peculiarity 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.

Many scientists have theorized that tanning occurs when ultraviolet radiation strikes the nuclei of melanocytes, causing DNA damage that prompts the melanocytes to produce pigment. This supposition, however, conflicted with the results of lead researcher Dr David Fisher's experiments. "Our work suggested that a peculiarity in the MC1R receptor on melanocytes is responsible for a failure to tan," Fisher relates. "But that sort of change on the cell surface shouldn¡¯t impede UV radiation from reaching the melanocyte¡¯s DNA."

The new experiments demonstrated that, rather than acting directly on the nuclei of melanocytes, UV radiation acts on keratinocytes (the most abundant as well as superficial cells in the skin), causing them to produce and secrete MSH, which attaches to adjacent melanocytes and starts the pigment-making process.

While Fisher's model adequately explains why redheads do not tan, it isn't the only possibility. "Suppose that during the embryonic or fetal period MC1R never activated cAMP production in developing melanocytes," Fisher proposes. "Would mature melanocytes then be permanently 'crippled,' unable to respond to UV, regardless of how its signals were transmitted?¡±

One way to disprove that "permanently crippled" scenario would be to see if melanocytes with abnormal MC1R receptors can be coaxed into producing pigment in adult mice. To attempt this, Fisher and his associates treated the skin of red-haired, fair-skinned mice with a compound known to increase cAMP levels. The compound, called forskolin, is derived from the root of the forskohlii plant found in India. The mice involved in the experiment turned 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.

The Dana-Farber researchers also showed that tans acquired through forskolin conferred significant protection against skin cancer caused by exposure to UV light. Fisher notes that while it is unknown whether forskolin will penetrate deeply enough in human skin to activate melanocytes, these results suggest that the search for other substances that do reach deep into the skin may well have the same pigmentation effects in people.

"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."