Melanoma Madness The scientific flap over sunscreens and skin cancer Chemical studies The parallel rise in skin cancer and sunscreen use has prompted chemists to reexamine the behavior of the products' active ingredients. Because sunscreens absorb light energy and must then release it in some form, they may deliver damaging ultraviolet (UV) radiation to sensitive cells. That raises the troubling, but unproved, possibility that sunscreens may have a hand in promoting skin damage. To learn more, chemists are testing sunscreens' responses to UV light. "Since [sunscreens] are so widely used, it is important to know as much as possible about them," says John Knowland of the University of Oxford in England. Surprisingly few reports on the chemistry of sunscreens have been published, says John M. Allen of Indiana State University in Terre Haute. So far, cosmetics companies have done most of the work, and they generally don't make their results available. "Sunscreens have -- at least in theory -- the potential to inflict damage. That is, of course, a far cry from saying that they actually do inflict this damage in humans," says Knowland. Are they beneficial or harmful? Indeed, that's the burning question researchers want to answer. The sun bathes Earth in UV rays -- short, energetic wavelengths of light that can damage cells. Most of the UV light that reaches Earth falls in the ultraviolet A (UVA) range, having wavelengths of 320 to 400 nanometers (nm). Such rays penetrate deep into the base layer of the skin, or dermis. Less of the light that reaches Earth's surface is in the ultraviolet B (UVB) range, with wavelengths of 290 to 320 nm. This light doesn't penetrate skin as deeply as UVA light, but it is more damaging. Scientists have only recently started paying attention to UVA radiation, once known as "tanning rays" in contrast to UVB's "burning rays." Tanning booths, for example, emit mostly UVA light. Researchers now know that UVA radiation both tans and burns the skin. Moreover, both UVA and UVB play a role in initiating skin cancers -- UVB by damaging DNA and UVA by suppressing the immune system. With the skin's defense and repair mechanisms held in check, damage goes unrepaired, thus leaving the door open for cancers to develop. Sunscreens prevent UV light from reaching the skin in one of two ways -- by absorbing it or by scattering it. Active ingredients such as Padimate O, octyl methoxycinnamate, and octyl salicylate absorb primarily UVB rays. The first sunscreen developed, para-aminobenzoic acid (PABA), fell out of use because it stained clothing and was found to cause allergic reactions in some people. Last year, FDA approved avobenzone, also known as Parsol 1789, as a UVA absorber. Other substances, such as titanium dioxide and zinc oxide, can scatter both types of UV light. So-called chemicalfree sunblocks often contain these compounds, as did the white paste that decorated the noses of lifeguards years ago. Sunscreens today use smaller titanium dioxide particles, which are invisible. Most sunscreen formulations contain a mix of these compounds to provide broad-spectrum protection over UVA and UVB wavelengths. If sunscreens absorb light, they must also re-emit it. "They cannot destroy that energy, they can only convert it to some other form," says Knowland. Moreover, scattering compounds that reflect light off the skin also redirect some of it onto the skin. When exposed to UV light, a sunscreen's active compounds interact with inert ingredients and with each other, as well as with the skin. The first step in deciphering this complex interplay is to conduct test-tube studies of the chemicals involved. The results may not reveal what sunscreens actually do on the skin, but they do indicate what sunscreens are capable of doing -- "so that if you want to examine what these chemicals might do in a realistic situation, then at least you know what to look for," Knowland explains. In the early 1980s, researchers demonstrated that PABA increases the formation of a particular DNA defect in human cells. This defect occurs when two adjacent molecules of thymine, one of the four bases of DNA, link together chemically to form a dimer. People who lack the mechanism to repair these defects are more susceptible to skin cancer, says Knowland. "Thymine dimers in your DNA are bad news." Last year, Knowland and Oxford colleague P.J. McHugh found in test tubes and in laboratory-grown human cells that Padimate O, a derivative of PABA, does not generate such thymine defects. However, it does oxidize DNA, and it produces free radicals that break DNA strands. Titanium dioxide and zinc oxide create similar strand breaks. Aware of the compounds' potency, manufacturers coat the sunscreen particles to make them less active. "These treatments do indeed reduce the activity," Knowland notes, "but they don't seem to eliminate DNA damage altogether." Experiments have shown that sunscreen-protected skin seems to suffer less DNA damage than unscreened skin, notes Frank Gasparro of Thomas Jefferson University in Philadelphia. "However, DNA damage isn't the only thing that contributes to skin cancer." In recent years, dermatologists have also become concerned about sunlight's ability to suppress the immune system, but little is known about this effect. Knowland says that hydroxyl radicals probably caused the DNA strand breaks he observed in his laboratory experiments. Allen adds that oxygen radicals, while not as reactive, can also harm DNA and other cell components. In collaboration with Sandra K. Allen, he used a filtered lamp that simulates sunlight to illuminate various sunscreens and gauge their ability to produce oxygen radicals. That ability varied widely. PABA generated oxygen radicals most readily, whereas benzophenones, such as oxybenzone, and salicylates appeared to produce none. "They are not equal," Allen says. Based on these results, however, Allen hesitates to recommend any one sunscreen over another. The picture gets even more complicated when one considers how the sunscreens interact with the radicals they have generated. "The sunscreen actually forms oxygen radicals that we would like to protect the skin against, but sunscreen also reacts with and traps them," mitigating harmful effects, Allen speculates. Some scientists argue that it is by trapping radicals that sunscreen blends offer their protection, he notes. No one knows whether sunscreens form oxygen radicals under real-world conditions, nor, if such radicals do form, whether they would damage living cells, Allen cautions. Much of the debate rests on whether a given sunscreen penetrates the skin. If it stays on the outermost layer, the epidermis, the effects of free radicals may not matter, since the epidermis is made of dead skin cells, says Allen. If a sunscreen penetrates the epidermis, enters the underlying cells, and is then excited by UV light, the picture becomes more disconcerting. Studies have shown that skin does absorb certain sunscreens. The breakdown products of PABA, for example, can be detected in urine, Knowland says. The same is true of the UVA absorber oxybenzone, researchers from the University of Queensland in Australia reported in the Sept. 20, 1997 Lancet. Schering-Plough Health Care Products in Memphis, Tenn., manufacturer of several brands of sunscreen, countered in the Feb. 14 Lancet that the amount of absorbed compound the Australian team detected was too small to be harmful. UV-scattering compounds don't sidestep the question of absorption either. Reducing the size of titanium dioxide particles to make them invisible could also enable them to enter cells more easily, Knowland suggests. "As far as published literature is concerned, my own personal view is that this question has not been adequately addressed yet." "The bottom line is, are sunscreens a good thing or not?" Most experts would say yes, perhaps dismissing as irrelevant the effects observed in the laboratory, Knowland continues. "They may turn out to be right, but my own view is that you have to continue to explore that before making an absolutely definitive pronouncement." "Wishing for a result isn't going to get that result," Gasparro remarks. "More research and understanding of basic science and biology in the skin -- that's going to tell us what's going on."