DNA damage to skin continues for hours after UVA exposure ceases, and melanin is a key culprit in the process, based on the results of cell cultures and studies in mice.
“What is extraordinary about this study is that it implicates melanin as a potential source of oxidative stress, [which can] lead to DNA damage and ultimately accelerate skin aging and skin cancer,” said Dr. Adam Friedman, director of dermatologic research at Albert Einstein College of Medicine, New York, who was not involved in the research. “For years, melanin was thought of as only a UV radiation protectant and antioxidant. Could this be a missing element in our fight to prevent skin cancer? The emphasis has always been on preventing the fire, not necessarily putting it out.”
Dr. Adam Friedman
The findings suggest that antioxidant-rich lotions might one day help prevent damage if users apply the “quenchers” soon after sun exposure, said lead author Sanjay Premi, Ph.D. at Yale University in New Haven, Conn., and his associates. Vitamin E and ethyl sorbate are two possible candidates for such “evening after” sunscreens, the researchers said (Science 2015 Feb. 20;347:842-7). For their study, the researchers exposed mouse fibroblasts and melanocytes to UVA, the main type of cancer-causing radiation from sunlight and tanning beds. Then they measured the accumulation of cyclobutane pyrimidine dimers (CPDs), a hallmark of UV-induced DNA damage. Levels of CPDs peaked immediately after UVA exposure in skin cells from albino mice, but kept rising for at least another 3 hours in melanocytes from pigmented mice, the investigators reported. Furthermore, 2 hours after live mice were exposed to UVA, their CPD levels were three times greater than just after UVA exposure, they said. “If the same holds for human skin, this would mean that past measurements of CPDs immediately after UV exposure have underestimated the consequences of UV exposure,” the researchers concluded.
They found similar results for human melanocytes, except that CPD levels varied more, probably because of genetic differences among human skin donors, Dr. Premi and his associates wrote. Further testing of melanin fragments revealed the process by which DNA damage accumulates, even after UVA exposures ends: Reactive oxygen and nitrogen species together excited an electron that in turn damaged DNA in the same way that UV radiation did. “A consequence of these events is that melanin may be carcinogenic as well as protective against cancer,” the researchers emphasized. “This double nature would explain the apparent cancer-facilitating effects of melanin seen in mice and in human epidemiology.”
Although “it is difficult to translate cell assays and mouse models to the human system,” the findings “no doubt raise important, paradigm-shifting ideas in terms of our understanding of UV-induced DNA damage,” said Dr. Friedman. For example, studies have shown that skin cells incur DNA damage even when individuals wear sunscreen as directed, he noted. “Are these cellular changes a result of sunscreen inefficiency, or is it delayed damage due to persistent melanin radicals?” he asked. “We see patients all the time who say, ‘I used sunscreen but I still got burned.’ Granted, there are likely many confounding factors, such as amount of sunscreen applied, frequency, clothing choice, and water exposure. However, maybe we can add progressive and persistent oxidative stress to the list.”
Developing effective “evening-after” lotions to halt UVA damage after exposure will take work, Dr. Friedman added. “The reality is that many, if not most, antioxidants are highly unstable, whether they oxidize easily when exposed to air, or are photo-labile, meaning they degrade upon exposure to sunlight,” he said. One solution is to encapsulate antioxidants within liposomes, solid lipid nanoparticles, or polymeric nanoparticles, but “skin penetration is not the only issue,” he added. “These antioxidants need to actually get into the cells to be effective.”
For that reason, researchers have explored systemic administration of agents such as polypodium leucotomos, which has antioxidant and anti-inflammatory properties, Dr. Friedman noted. “The clinical data available looks at using this natural ingredient to increase minimal erythemal dose, rather then postirradiation recovery,” he said. “Could postirradiation intake be effective? Possibly.”
The research was funded by the U.S. Department of Defense, the National Institutes of Health, the University of Veterinary Medicine in Vienna, Fundação de Amparo à Pesquisa do Estado de São Paulo, and INCT–Processos Redox em Biomedicina. The investigators declared having no conflicts of interest.