Stepping out of the sun—or rising from a tanning bed—won’t spare your skin. The harm that UV light inflicts on the DNA is sustained for hours. UV light, it turns out, may act via a “light” or a “dark” biochemical pathway to cause a type of DNA damage known as a cyclobutane pyrimidine dimer (CPD). CPDs accumulate in melanocytes, the cells that make the melanin that gives the skin its color.
In the past, experts believed that melanin protected the skin by blocking harmful UV light. But there was also evidence from studies suggesting that melanin was associated with skin cell damage. Now it appears that although melanin offers protection while the sun is shining, it participates in CPD formation that occurs via the dark pathway. That is, melanin takes part in chemical reactions that result in “dark CPDs.”
This finding emerged from a study conducted by scientists at Yale University. These scientists, led by Douglas E. Brash, Ph.D., a clinical professor of therapeutic radiology and dermatology, exposed mouse and human melanocyte cells to radiation from a UV lamp. To the scientists' surprise, the melanocytes not only generated CPDs immediately but continued to do so hours after UV exposure ended. Cells without melanin generated CPDs only during the UV exposure.
The study appeared February 19 in Science, in an article entitled, “Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure.” According to this article, chemiexcitation, a relatively slow process previously seen only in lower plants and animals, may also occur in our skin cells. Specifically, UV light induces reactive oxygen and nitrogen species, which excite an electron in melanin fragments. Then the fragments nonradiatively pass the excitation energy to DNA, producing a CPD. In a CPD, two DNA “letters” attach and bend the DNA, preventing the information it contains from being read correctly.
The researchers described how they tested the extent of damage that occurred after sun exposure by preventing normal DNA repair in mouse samples. Also, they reported how they found that half of the CPDs in melanocytes were dark CPDs.
“We found that in melanocytes, CPDs are generated for >3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds,” they wrote. “Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner.”
While noting that news of the carcinogenic effect of melanin is disconcerting, the researchers also pointed to a ray of hope: The slowness of chemiexcitation may allow time for new preventive tools, such as an “evening after” sunscreen designed to block the energy transfer. This point was expanded upon by John-Stephen Taylor, Ph.D., a chemist at Washington University, St. Louis, who contributed a perspective piece (“The dark side of sunlight and melanoma”) that accompanied the research article in Science.
“As suggested by the authors, UV DNA damage arising in the dark might also be reduced by agents that scavenge or interfere with superoxide and nitric oxide production, or that quench the excited triplet-state intermediates,” Dr. Taylor wrote. “It is intriguing to speculate as to whether oxidatively generated DNA chemisensitizers may also be playing a role in the induction of cancers in tissues not exposed to light, which could thus benefit from similar intervention.”