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Sunbathers: Beware the A-ray
27 June 2007
NewScientist.com news service
Jessica Marshall

Enlarge Melanoma risk

SUMMER is here, at least for those of us on the top of half the world. It's time to dump the coats, bare the shoulders and bring on the barbecues, time for days at the beach, outdoor sports and fun in the sun. And thanks to the miracle of modern chemistry known as sunscreen, we can spend hours under the sun without worrying about the consequences.

Or can we? The incidence of the most deadly form of skin cancer, melanoma, is increasing faster than that of any other cancer, doubling every one or two decades in countries such as the US, UK and Australia. There's no doubt that more people exposing more skin to the sun more often is the underlying reason behind the huge rise since the 1950s. Yet when epidemiologists began to look at the effects of sunscreens in the 1990s, they found no evidence that these creams and lotions were reducing the impact of our love of sunshine by protecting us from melanoma.

How is this possible? While sunburn is mostly caused by the part of the ultraviolet spectrum known as UVB, there's growing evidence linking melanomas to UVA. Older sunscreens allowed people to stay out in the sun longer without burning but provided little protection against UVA, so they increased people's exposure to these wavelengths.

If UVA really is responsible for melanoma, a whole generation may have been misled into thinking sunscreens allowed them to soak up the rays with impunity. Lawyers in the US have filed a class action lawsuit against a number of sunscreen makers alleging that labels such as "sunblock" are misleading, because the products do not "block" the whole UV spectrum and often imply equal UVA and UVB protection.

Most newer sunscreens do now provide some protection against UVA, but there is no uniform standard for measuring this protection, so it's hard to know what you are buying. What's more, even the best modern sunscreens don't seem to provide enough protection against the harmful effects of UVA. Are we all better off putting on a hat and shirt before reaching for the sunscreen?

This is a hard question to answer, because it's still not clear exactly what causes melanoma. The sun is the major risk factor and there is good evidence that if you get sunburnt often, especially in childhood, your risk of developing melanoma rises. Having red hair or a lot of moles also increases the risk.

Beyond this, the picture gets murky. The key question is the relative importance of UVA and UVB. UVA is the part of the electromagnetic spectrum just beyond visible light, usually defined as having a wavelength of 400 to 320 nanometres. UVB is the next part, from 320 to 280 nm. In terms of overall energy, the sunlight reaching your skin can contain anything from 10 to 100 times as much UVA as UVB, depending on your latitude, altitude, the time of day and the state of the ozone layer. Yet despite there being so much less of it, UVB with its shorter wavelengths and more energetic photons is overwhelmingly responsible for sunburn. This means that the SPF sunscreen rating system, which is based on how long it takes for a mild sunburn to develop on human skin, is primarily a measure of UVB protection.

Because of its ability to cause sunburn, UVB was long blamed for all skin cancers too, but when it comes to melanoma there are reasons to suspect UVA. For starters, skin is more transparent to UVA, so the rays penetrate deeper, reaching the base of the epidermis where the pigment-producing cells called melanocytes sit. It's the melanocytes that can form melanomas.

Yet pinning down the blame is far from easy. It is practically impossible to work out how much UVA versus UVB people are exposed to in their lifetime, so epidemiological studies are not much help. However, one clue comes from the fact that UVA levels do not decrease at higher latitudes by as much as UVB levels, and the same pattern is seen in the incidence of melanoma compared with other skin cancers.

Though few animals develop human-like melanomas, they do occur in a platyfish hybrid specially bred to develop them. When Richard Setlow of Brookhaven National Laboratory in Upton, New York, was studying these fish, he kept some in a greenhouse, where they were exposed only to UVA - since glass filters out UVB but allows UVA through. Some of these fish developed melanoma, and Setlow went on to show that UVA and visible light were responsible for 90 per cent of melanomas in fish exposed to normal sunlight.

The types of mutations found in melanoma cells are also consistent with UVA damage. UVB can break the rungs of DNA strands, producing characteristic mutations. Melanomas, however, tend to have mutations more typical of the oxidative damage caused by reactive free radicals, which UVA generates in the skin. These free radicals may also be largely responsible for the ageing effect sunlight has on skin.

The work of Edward De Fabo of the George Washington University Medical Center in Washington DC, however, challenges the idea that UVA can trigger melanoma. His team has been working with a strain of albino mice that develop human-like melanomas if exposed to UV as newborn pups. Only UVB causes melanomas in these mice (Cancer Research, vol 64, p 6372).

This seems to contradict all the evidence pointing to UVA, but supporters of the UVA hypothesis point out that the albino mice are a poor model for human melanoma because they lack melanin - which may play an important role in the disease. The argument goes like this. Melanin pigments protect against all UV by absorbing it before it penetrates too deeply, but there is a price to pay: melanin can also be oxidised by UVA and UVB, forming melanin radicals, which then generate other kinds of radicals. If these radicals really do trigger melanoma, then a lack of melanin in melanocytes should have a protective effect - and sure enough melanoma is extremely rare in people with albinism.

Yet if melanin radicals lead to melanoma, why are rates of the cancer lower in people who tan easily, and lower still in people with black skin, De Fabo asks. The clue could lie in the observation that people with red hair are more likely to develop melanoma, says David Fisher of Harvard University. Redheads make only one of the two main types of melanin, a red-yellow pigment called pheomelanin. They cannot make black-brown melanin, or eumelanin. Pheomelanin is the less stable of the two and is more likely to generate radicals. Non-redheads have both types of pigment, but produce more eumelanin when they tan. "You could imagine that the benefit of a tan is that it is switching the ratio from high pheomelanin/low eumelanin to higher eumelanin, which may explain why very dark-skinned people or people who tan are less likely to develop melanoma," says Fisher.

De Fabo is now testing the idea that it is the combination of UVA and melanin that leads to melanoma by studying pigmented mice. There is already some evidence for this. In a study published last year, melanin radical formation in the skin cells of platyfish was measured using a method developed by Graham Timmins, a photobiologist at the University of New Mexico in Albuquerque. The team found the UV wavelengths most likely to induce radical formation were the same as those likely to cause melanoma (Proceedings of the National Academy of Sciences, vol 103, p 4111). "It's not definitive, but very supportive," Timmins says.

Crucial threshold

He proposes that up to a certain level of exposure, skin cells can mop up the all free radicals formed by sunlight. Beyond this threshold, however, oxidative damage occurs. In people with a tan or dark skin, less UVA reaches the melanocytes and it is less likely to generate radicals because there is more eumelanin, so they can spend longer in the sun before suffering serious damage. The opposite applies to those with pale skin, which would explain why occasional but intense exposure to sunlight - those holidays in the sun - increase the melanoma risk.

If this picture is right, a tan might offer better protection against melanoma than a sunscreen. However, Fisher stresses that it's not worth risking the UV exposure required to get one. Instead, he is working on ways to induce a natural tan without sun exposure (New Scientist, 10 March, p 34). In the meantime, short of covering up altogether, a sunscreen with good UVA protection would seem to be the best defence.

Most sunscreens do now provide some protection against UVA. Some manufacturers add physical blockers such as zinc oxide or titanium dioxide, which scatter and absorb both UVA and UVB. Others contain organic molecules designed to absorb UVA energy.

There are issues with some of these ingredients. For instance, to keep physical blockers from being visible on the skin's surface - the warpaint effect - the particles must be very small, and there are concerns about the safety of such nanoparticles. The main issue, though, is whether newer sunscreens really do provide sufficient UVA protection. At the moment, there are no consistent standards for measuring UVA protection equivalent to the SPF rating. Regulators in the US, Australia and many European countries are still debating what standards should be used.

Some favour the star system devised by the British company Boots, which measures the ratio of UVA to UVB absorption by a certain thickness of sunscreen on a plastic surface. To earn a four-star rating, for instance, the UVA absorbance must be at least 80 per cent of the UVB absorbance for a given product. Timmins points out, though, that this testing method doesn't necessarily represent how sunscreen will behave on skin - after water exposure, for instance. Most people also apply far less sunscreen than makers recommend.

What's more, even those sunscreens rated highest by the star system may not provide enough protection against the damaging effects of UVA. In 2003, a team at Mount Vernon Hospital in London measured levels of ascorbate - formed when free radicals react with vitamin C - in pieces of human skin exposed to UV. Two sunscreens with an SPF of over 20 and a four-star UVA rating were applied to some pieces. If UVA protection was 80 per cent of the UVB protection, as the four-star rating suggests, you might expect ascorbate levels to fall at least 16-fold. In fact, they fell just 50 per cent.

A study by Timmins published earlier this year came to broadly similar conclusions. In tests on animal skin, he looked at how much various sunscreens reduced melanin radical formation at specific wavelengths. A commercial SPF 30 sunscreen containing the UVA-blocker avobenzone reduced melanin radical production at UVB wavelengths by as much 34-fold, in line with its SPF. Yet at UVA wavelengths, melanin radical production fell only 13-fold, less than half the UVB equivalent.

These results suggest that even modern sunscreens with much better UVA protection have the same fundamental problem as older ones. "You're still going to be selectively increasing your UVA exposure if you just rely on sunscreen," Timmins says. The fact is that people using sunscreens with high SPF factors tend to stay in the sun longer, even in experiments where they haven't been told what the exact SPF factor is. This means sunscreen users end up getting a higher dose of UVA than those who do not use a sunscreen and spend less time in the sun. "You may be avoiding burning, but you may be piling on more free radicals because of this kind of exposure," says Richard Gallagher, a dermatologist at the University of British Columbia in Vancouver, Canada.

Timmins would like to see UVA protection ratings based on measurements of melanin radical formation in skin. If melanin radicals are indeed the primary cause of melanoma and ageing, this is a much more direct way to measure protection against the negative effects of UVA than other methods. It might also give manufacturers more of an incentive to produce sunscreens with more effective UVA protection.

Improving UVA protection brings some practical problems, though. In particular, since the UVA spectrum butts up against the visible spectrum, it is hard to mop up all the UVA without soaking up some violet/blue light, so a cream that absorbed these wavelengths would make people look unacceptably yellow.

So what should you do this summer? While there is as yet no rock-solid proof that UVA causes melanoma, there is certainly good reason for caution. No one is saying don't use sunscreen, but slipping on a shirt and slapping on a hat will give you far more protection.

To complicate things further, there are some researchers who think the "avoid the sun" message has gone too far. They advise moderate exposure, because the vitamin D our skin makes when exposed to UVB may reduce the risk of many cancers. Even if they're right, though, you don't need much sun to get enough vitamin D: in London in the summer, for instance, exposing your face and arms without sunscreen for just 10 minutes a day is sufficient for those with pale skin.

What's clear is that spending hour after hour soaking up the sun when you're on holiday is a bad idea, no matter how much sunscreen you slather on. Look on the bright side: staying in the shade will keep you looking younger in years to come - and you might well live longer too.

From issue 2610 of New Scientist magazine, 27 June 2007, page 38-41

Hooked on UV However damaging it may be, there's no denying the pleasure of soaking up the rays. In fact, it feels so good that some people may become addicted. One of the by-products of the tanning process is beta-endorphin, the feel-good, pain-reducing neurotransmitter that we release when we exercise, laugh or have sex. When dermatologist Stephen Feldman learned of this, he wondered if some of his patients were hooked. "That would explain why they go to the tanning beds," he thought. "They go every day, they look horrible, their skin is wrinkled and mottled. Yet they say, 'It feels so good. It's so relaxing.'" In one study, Feldman, who is at the Wake Forest University School of Medicine in Winston-Salem, North Carolina, gave sunbed users increasing doses of naltrexone, which blocks the endorphin receptor, or a placebo. Strikingly, half of the frequent tanners exhibited symptoms of withdrawal after taking naltrexone. A study by another team, based on questionnaires, concluded that one-third of frequent sunbed users showed signs of addiction.

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