UVA vs UVB

Following on from my previous post on the inanity of anti-sun public health campaigns, I wanted to discuss a few aspects of sunlight itself and pathophysiology of melanoma.

Here is the story so far:

– the relationship between sunlight and melanoma is complicated. Genes matter (your family history), your phenotype (skin and eye colour) can be a risk factor, but the environment also seems to play a large role.

– there is no linear relationship between exposure and melanoma. Zero exposure over a lifetime will probably guarantee no melanoma (I’ll leave it up to you if you would like to spend your life hidden inside because let’s face it, what could possibly go wrong?) But beyond that, the picture is sketchy. Less exposure does not mean less melanoma. Chronic UV exposure has been repeatedly shown to be protective.

– in spite of widespread and very successful health campaigns which focus on one single risk factor (sunlight) the incidence of melanoma is rising.

– while it is tempting to reduce exposure to minimum in an attempt to mitigate risk, the lack of sun exposure is a significant problem on its own. I won’t go into too much detail here, but vitamin D deficiency (which is estimated to affect 1/3 of Australians)  is only a part of the picture.

Sunlight is frequently referred to as some homogenous substance in the same way that all fat is apparently the same because each gram contains the same number of calories. However, just like lauric acid (a medium chain saturated fat) is processed in your body completely differently from palmitic (long chain saturated) or DHA (long chain omega-3), different wavelengths of solar spectrum have varying effects on our physiology.

UV radiation is only a part of solar spectrum, with wavelengths between those of X-rays and visible light. Its unique effect on biological systems stems from the ability of the photon  to break chemical bonds. UVR is further divided into UVA (the longest wavelength at 400 – 315 nm), UVB (315 – 280 nm) and UVC (280 – 100 nm). While the shorter wavelengths of UVC and UVB are most damaging to biological entities like human cells, they are also filtered by our ozone layer. In normal run of things UVC is completely blocked with none of it reaching the Earth’s surface. UVB is blocked partially with the rate of absorption proportional to the length the photon travels through the ozone layer. If you got a little lost in the last sentence here is the gist. If the sun was directly over your head and the sun rays were falling at 90 degrees to the surface of the Earth (this is considered Solar Zenith Angle of zero), photons would have to travel the shortest distance through the ozone layer and more UVB radiation would reach the surface. If the direction of the radiation is at 45 degrees to the surface, more ozone is encountered on the way and less UVB gets to the surface.

Ok, with maths out of the way let’s get to the nitty gritty of what is different between UVA and UVB.

skin penetrationWhile UVB is a stronger partner being able to cause direct damage to DNA, it is also the one that has less penetration. In fact, very little is able to penetrate down to the basal cell layer where melanocytes live.

UVAWhat is this “photoprotection” I am talking about? Amazingly enough, after millions of years under that yellow orb our bodies did not wait for the invention of sunscreens. Instead, we have evolved multiple ways to protect ourselves. Locally in the skin, there are two major mechanisms of photoprotection.

  1. Skin thickening. Sounds too simple to be effective but it does in fact work, especially in preventing UVB penetration. This effect is mediated most strongly by UVB itself and manifests in thickening of stratum corneum.
  2. Melanin production. Melanin is a substance produced by the melanocytes in the basal cell layer. It absorb UVR as it passes through the skin and prevents further damage. It is an excellent defender against both UVA and UVB rays. The initial DNA signal is required for the initiation of melanin production. Here is where the differences between UVA and UVB are most striking. Even though the tan produced by UVA and UVB looks identical, its origins are different. UVA does not increase total content of melanin in the skin, it just releases pre-made melanin from the melanocytes and oxidises it. UVB, on the other hand, stimulates melanin production.

So if you predominantly expose your skin to UVA rather than UVB you may be getting sun damage without the benefit of innate skin protection.

UVB used to get a lot of bad rap. And who could blame the scientists doing in vitro experiments and seeing DNA molecules unravel, the sequence misread, uncontrolled proliferation initiated – all in response to UVB. In fact, we have done everything we could to eliminate our exposure to UVB rays full stop. SPF rating of sunscreen applies to its ability to prevent erythema, aka burn. Therefore it reflects how much UVB it can block (UVB being the erythematogenic partner).

UVA remained under the radar for a while. Solariums used to be advertised as “safer than the sun” because UVA was predominantly used. Now UVA is coming more under suspicion for being the culprit behind melanoma. How to tease out which is which? For starters, scientists like to use some poor animals to prove their theories.

It is hard to believe but we haven’t got very decent animal models of melanoma. Well, there is this fish which got melanoma after being irradiated with UVA.

…an alternate action spectrum that is more heavily weighted to the longer wavelengths, including UVA and visible light, has been found in the platyfish-swordtail hybryd model of melanoma, which suggests that UVA is a much more potent inducer of melanoma, relative to UVB, than it is of tanning. The relevance of this animal model to human melanoma is uncertain but cannot be completely discounted because of its particular characteristics and phylogenetic distance; development of mammalian models will be particularly informative in this regard.
Weinstock (1996) Controversies in the Role of Sunlight in the Pathogenesis of Cutaneous Melanoma. Photochemistry and Photobiology, 63(4) 407

And there is this knockout mouse which got melanoma after being irradiated with UVB. http://www.nature.com/jidsp/journal/v10/n2/full/5640184a.html

These data show that in this albino mouse model UVB is responsible for the induction of melanoma, whereas UVA is ineffective even at doses considered physiologically relevant.
Ha L. et al (2005) Animal Models of Melanoma. Journal of Investigative Dermatology Symposium Proceedings, 10, 86–88;

Go figure. I would not be relying on the evidence from a fish and a GMO mouse as yet. Give me some humans. Well, actually, you can infer some information on which wavelength initiated melanoma by looking at what mutations are associated with this cancer in humans. As you remember (scroll up to the graphic if you don’t), UVB causes CPD and 6-PP product formation. UVA is the initiator of free radical formation. After going through the known signature mutations in humans, Lund et al concluded:

Thus it can be seen that, although not yet incontrovertible, the available evidence points away from pyrimidine dimer formation by UVB and toward oxidative stress damage caused by longer wavelengths [UVA].
L.P. Lund, G.S. Timmins (2007) Melanoma, long wavelength ultraviolet and sunscreens: Controversies and potential resolutions. Pharmacology & Therapeutics, 114: 198–207 (my square brackets)

The As have it?

Another crucial component to add to the mix is Vitamin D. Without going to far into this massive topic, I will just mention that it is one of our main immunomodulators, both preventing DNA damage and initiating repair and/or apoptosis (programmed cell death) when necessary. Its active form, 1.25(OH)2D, is protective against UVR-induced photocarcinogenesis. In diagnosed melanoma, Vitamin D levels and pre-cancer skin exposure are predictive of survival. Not forgetting that UVA does not lead to vitamin D synthesis. In fact, it can break it down when it is attached to the vitamin D receptor (VDR). You need UVB in order to synthesise Vitamin D in your skin.

So here you go. When it comes to sunlight, things are not always what they seem. Focusing our full attention to blocking ALL sunlight to protect ourselves, we may have unwittingly increased our UVA to UVB ratio.

UVA and UVB imbalance is a neat hypothesis. It resolves some of the apparent paradoxes relating to sunlight and melanoma, the paradoxes that conventional wisdom desperately tries to ignore.

To summarise: what are the effects of receiving too much UVA and not enough UVB?

  • Reduced propensity to sunburn
  • Reduced melanin production – > reduced photoprotection
  • Reduced Vitamin D production
  • Increased Vitamin D breakdown

And how to you ensure you upset this balance in favour of UVA?

  1. Wear sunscreen that predominantly filters UVB
  2. Consequently stay out in the sun too long because your sunscreen prevents you from burning so you continue to receive UVA without a burning signal to get your ass in the shade
  3. Go out in the sun early in the morning and late in the afternoon and avoid midday hours (when you actually get some UVB exposure)
  4. Get a “safe tan” in the solarium
  5. Stay indoors and get all your sunlight through the window (UVA gets through the glass, UVB doesn’t).

Sounds like something we have been doing for the last 30 years.

So do we still think that there is not such thing as safe tan? Or that sunscreens will save us all?

 

The Dark Side of Anti-Sun Campaigns

AHS13 has been and gone. Hideous trans-Pacific jetlag is now over. I am off Twitter and other social media, apart from our Whole9 South Pacific page as part of our Personal Growth September (Jamie calls it the Antisocial Media September). I will write a post on it another day to explain why we decided to surrender to our antisocial introverted selves. The main benefit of not spending wasting time scrolling through a Twitter feed is time to think and time to write. I have come to the conclusion that my 20 minute presentation on melanoma at AHS was grossly inadequate to explain my thoughts and conclusions regarding sunlight and melanoma.

I first became interested in sunlight when I was preparing an Honours project on Vitamin D and Multiple Sclerosis in medical school. I never published but I kept the research, as well as the overall feeling that sunlight is good, is necessary, and is sometimes healing. This is in contrast to what I can only describe is the state of fear when it comes to the UV radiation in Australia. This paranoia is incredibly pervasive*. Those of you who do not live Down Under might not appreciate its true extent. Otherwise sensible adults get a look of panic in their eyes when melanoma is mentioned. Children at school are not allowed outside into the sun at recess or lunch unless they wear a wide-brimmed hat. Those whose irresponsible parents dare to forget one, stay in the shade, unable to play. Every preschool and school excursion involves long sleeved rasher shirts, tubs of sunscreen applied liberally on each child and, again, hats.

*I am not talking about whether this is clinically justified as yet, merely describing the situation.

The public awareness campaigns are omnipresent. The iconic Slip!Slop!Slap! campaign launched in 1981 is widely touted as one of the most successful campaigns in the Australian history. From the SunSmart website:

Cancer Council believes its Slip! Slop! Slap! campaign has played a key role in the dramatic shift in sun protection attitudes and behaviour over the past two decades.

Wow! That’s fantastic. That campaign must have saved thousands of lives and stopped cancer in its tracks! From Melanoma Institute Australia website:

Melanoma rates have doubled in the 20 years from 1986–2006.

Awkward.

It is quite fascinating that most people in Australia like to talk quite expertly on the topic of melanoma. We are so well “educated” by various health campaigns that any self-respecting TV owning Aussie off the street will tell you that sunlight causes melanoma. Total strangers will point out that the visible burn on your nose from the weekend SUP adventures is practically cancer waiting to happen. And heaven forbid you mention you had blister burns in childhood. People just shake their heads and look away, as if you are not long for this world.

I like to compare that unshakeable assurance to the society’s view on saturated fat. Your Auntie Madge just KNOWS that butter on your broccoli will clog up your arteries (while she is completely safe with her low fat banana bread) and cause a heart attack. Just like she KNOWS that going out in the sun without sunscreen will result in your untimely death.

Researchers in dermatology may argue about photocarcinogenesis for another 20 years. As far as the  public goes, the sun has already been condemned.

For those of us who have come to question and ultimately reject the conventional wisdom as it relates to the diet-heart hypothesis, it is almost too easy to reject this other “undisputed truth”.

It doesn’t help the cause of the sunlight fighters that they use emotional blackmail and scare tactics to “warn” the population about the dangers of that bright orb in the sky. Let me give you an example. For those of you living in Australia this will be very familiar as you have no doubt seen these “health announcements” on TV multiple times.

The self-professed aim of these campaigns is to discourage the pro-tanning attitude of the younger generation. I don’t know about you, but I feel quite uncomfortable about the imagery used in this commercial. A healthy cell transforms into a black tentacled monster which burrows its way into a blood vessel and multiplies, seeding the body with its progeny. Children will have nightmares. I realise this is a pictorial representation but this is not what happens. Hard-hitting messages are sometimes necessary but you need to be absolutely sure that your message is 100% backed up by solid evidence.

And this is where we hit a little snag.

This particular commercial seems to imply that tanning increases the risk of melanoma. Let’s examine this assertion in a little more detail.

1. Having a tan is generally associated with chronic sun exposure. Chronic (occupational) sun exposure has been repeatedly shown to be protective against melanoma (Elwood and Jopson, 1997).

2. Tanning and sunburn are two different things. The evidence on sunburn and melanoma is not foolproof but there seems to be a slightly increased risk.

3. The ability to tan is first and foremost influenced by your skin phenotype which is genetically predetermined. When it comes to melanoma, your skin phenotype is one of the recognised risk factors. In other words, those who are able to tan are at less risk than those (unfortunate redheads) whose skin seems to go from “pale blue” to “scorched red” to “ginger peel” with not a hint of a healthy glow. So the very fact that you are turning a nice chocolatey brown the minute you expose an inch of flesh may indicate that you have a favourable phenotype. But, of course, not everyone with skin type I develops melanoma either!

4. All tan is not the same. Although they look identical, skin tans induced by different UV wavelengths have different mechanisms. UVB-induced tan causes dramatic increases in melanin synthesis. In contrast, UVA has no effect on melanin content. The tan produced by UVA is due to the distribution and oxidation of pre-existing melanin precursors. (Miyamura et al (2011) The deceptive nature of UVA-tanning versus the modest protective effects of UVB-tanning on human skin, Pigment Cell Melanoma Res). Melanin = photoprotection. Hence UVA and UVB have totally different protective qualities.

Maybe to be on the safe side we should stay indoors and avoid the sun altogether. But it seems that those who work indoors and bask under the cool office lights are, in fact, at higher risk of melanoma.

Godar et al (2009) Increased UVA exposures and decreased cutaneous Vitamin D3 levels may be responsible for the increasing incidence of melanoma. Medical Hypotheses 72:434-443

“Paradoxically, although outdoor workers get much higher outdoor solar UV doses than indoor workers get, only the indoor workers’ incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate since before 1940.”

“In fact, outdoor workers have a lower incidence of CMM compared to indoor workers”

In diagnosed melanoma cases, previous exposure, intermittent or chronic, is associated with lower mortality. Which seems to make no sense at all if you subscribe fully to “sunlight causes melanoma” argument.

Rosso et al (2008) Sun exposure prior to diagnosis is associated with improved survival in melanoma patients: results from a long term follow up study of Italian patients. European Journal of Cancer 1275-1281

“Time spend on the beach during adulthood (on average 3 weeks/years for 19 years) was inversely associated with the risk of death…”

There are plenty of grey areas in the UV-melanoma story but tanning is certainly not one of them. I would love sending a public message to the organisation who sponsored the ad, requesting to show a single study linking suntan with melanoma.

Here is my new anti-Sun campaign suggestion. I think we are not far off that.