SUN DAMAGE AND PREVENTION
Mark F. Naylor, MD
Assistant Professor, Department of Dermatology
Center for Molecular Medicine, College of Medicine
University of Oklahoma
Kevin C. Farmer
Assistant Professor, Department of Pharmacy Practice
College of Pharmacy, University of Oklahoma
Sun Damage Sunlight Composition Harmful Effects of UV Radiation Sunburn & Acute Damage Subacute and Chronic UV Effects Immunologic Effects Ultraviolet and Carcinogenesis Ultraviolet and Melanoma Formation Melanoma Action Spectrum in Animals Melanoma Action Spectrum in Human Ultraviolet and Non-Melanoma Skin Cancer Sun Protection Strategies Sun Avoidance Protective Clothing Tanning Sunscreens Sunscreen Protection From UV Sunscreens & Aging Sunscreens & Immune Effects of UV Sunscreen Use and Skin Cancer Risk High SPF Sunscreens and FDA Safety of Sunscreens Section 1 Guidelines for Minimizing UV Exposure Assessment of Skin Types Advise on UV Protection Sunscreen Application and Use Summary
Our knowledge of ultraviolet radiation and it's effect on skin has increased rapidly in recent years. Repeated sunburns are now recognized as a major risk factor for melanoma, the most deadly form of skin cancer . Sunlight is the primary cause of skin aging, wrinkles, blotchy pigmentation and skin cancer [2-4]. In addition, many sun worshippers do not want to lose their seasonal "tan" and complement their sun exposure with tanning lamps from over 25,000 tanning parlors in the United States .
In practical terms, the biologically important output from the sun reaching the earth's surface can be divided into four wavelength regions, ultraviolet B (UVB, 280-315 nm), ultraviolet A (UVA, 315-400 nm), visible light (400-760 nm) and infrared (760-106 nm) . Ultraviolet wavelengths shorter than 290 nm are heavily absorbed by molecular oxygen, ozone and water vapor in the upper atmosphere and do not reach the surface of the earth in measurable amounts . All of the biologically important effects of sunlight are necessarily due to wavelengths in the 290-106 nm range. Except in special circumstances, such as photodrug reactions and certain disease states, visible light does not appear to be harmful to normal individuals. Infrared is essentially heat, and although non-solar sources can cause skin tumors and cataracts, it is uncertain at present if the infrared in sunlight contributes significantly to the problem of skin cancer [7-14]. Thus, the major source of the damaging effects of sunlight stem primarily from the ultraviolet portion of the spectrum between 290 and 400 nm (UVB and UVA) . The different ultraviolet wavelengths penetrate the skin to different depths and have different biologic consequences (Figure 1).
Ultraviolet A (UVA, commonly called "black light") is actually the most abundant component of solar ultraviolet radiation, accounting for approximately 95% of the ultraviolet energy striking the earth's surface at the equator. UVA is also the major wavelength produced by tanning beds, and has had a reputation in the past of being the so-called "safe" portion of the ultraviolet spectrum. Recent experimental evidence has made it clear that UVA exposure has significant risks, although it may not be as dangerous as UVB. However, UVA penetrates much deeper into the skin than any of the other ultraviolet wavelengths, and can potentate the carcinogenic effects of UVB. Possibly because of its ability to penetrate deeply into the skin, UVA contributes substantially to chronic sun damage, wrinkling and can cause immunologic effects [15-19].
Although UVB makes up only 5% of the ultraviolet photons reaching the earth's surface, it is the most important component of sunlight for human skin. It is considered the major action spectrum for both melanoma and non-melanoma skin cancer formation [20-22]. Although it does not penetrate as deeply as UVA, and does not interact as vigorously with the epidermis as UVC, UVB combines depth of penetration and reactivity with macromolecules in such a way that it is the most biologically potent portion of the UV spectrum in terms of short and long term consequences.
Harmful Effects of UV Radiation
The damaging effects of ultraviolet on skin consist principally of direct cellular damage and alterations in immunologic function. Direct effects include photoaging, DNA damage and carcinogenesis. When incident ultraviolet strikes human skin, it is absorbed at various wavelength-dependent depths by molecular species with the capacity to absorb it (protein, DNA, lipids, water). The sum of the photochemical interactions resulting from this absorption, combined with secondary interactions, notably with oxygen species, is ultimately responsible for UV-induced damage. Important aspects of these effects on the skin and immune system are discussed below.
There is general agreement that DNA is a principle target of UV-induced skin damage. The fact that the action spectrum of erythema is similar to the absorption spectra of DNA is consistent with this concept . Pyrimidine bases are more sensitive to UV damage than purines and undergo a number of photochemical modifications . Cyclobutane dimers formed from adjacent pyrimidines are a major form of direct UV-induced DNA damage . In addition to photoproducts, indirect evidence suggests that reactive oxygen species are responsible for some UV-induced DNA damage [24-28]. Recently, direct evidence of UV-induced reactive oxygen DNA damage has been demonstrated . One of the clinically detectable effects of ultraviolet damage that deserves particular attention is erythema, since this forms the basis of the current sunscreen potency measurement and has been correlated with melanoma risk.
Sunburn & Acute Damage
Sunburn is a popular term applied to the marked erythema and pain that commonly follows injudicious sun exposure. A sunburn is really a delayed ultraviolet B-induced erythema caused by an increase in blood flow to the affected skin that begins about 4 hours and peaks between 8-24 hours following exposure [23, 30, 31]. The underlying cause of this vascular reaction is direct and indirect damage to specific cellular targets from photochemical reactions and the generation of reactive oxygen species . Damage to DNA, and the activation of several inflammatory pathways, particularly involving prostaglandins [27, 33-38], are thought to trigger this reaction, ultimately leading to vasodilation and edema. Biologic response modifiers released by both keratinocytes and lymphocytes also play a role [39-55]. The development of erythema therefore implies that enough ultraviolet damage has occured that inflammatory pathways have been activated. Erythema is probably best thought of as a total failure of sun protection, and is a marker for severe UV damage.
Several lines of evidence suggest a relationship between erythema and DNA damage. There is rough correlation between pyrimidine dimer yeild and susceptibility to erythema with sun exposure . Wavelengths that are the most efficient at producing erythema are also the most efficient at producing pyrimidine dimers . From a scientific point of view, a sunburn can be viewed as a marker for a substantial ultraviolet over-exposure that has clinical implications for skin cancer risk. It is now appreciated that there is a linkage between a history of repeated, severe sunburn and increased risk for melanoma [1, 57-62] and non-melanoma skin cancer [63-65].
In the past there has been a presumption that erythema per se was linked to the carcinogenic effect of sunlight. Implicit in this was the assumption that UV exposure that did not induce erythema was harmless. While erythema-producing exposures probably are especially harmful, there is no particular reason to believe that non-erythrogenic exposures are safe.
In experimental mice, gradual (e.g. non-erythrogenic) doses of ultraviolet can be more carcinogenic on a per joule basis than doses given more rapidly (e.g. erythrogenic) . While erythema is linked to enhanced carcinogenic effect, it is probably not a requirment for carcinogenic effect. Mouse studies have demonstrated that both suberythemal UVB and UVA cause tumors [67-69]. In the Southwestern US it is not unusual to diagnose skin cancers in skin type 4-5 individuals with high cumulative lifetime UV exposures and no tendency for or history of repeated severe sunburns, suggesting that suberythrogenic neoplasia also occurs in humans.
Subacute and Chronic UV Effects
Chronic exposure to sunlight accentuates and accelerates many of the changes of intrinsic aging, including telangietasia, blotchy pigmentation, loss of elasticity, and thinning [70-72]. While thickening of the epidermis may be a short-term effect of sun exposure, the eventual result will be exacerbation of the age-associated thinning .
Abnormal pigmentation can take several forms. Indistinct and blotchy areas of hyper and hypopigmentation are commonly seen in chronically sun exposed skin . Hyperpigmentation and hyperpigmented lesions are more prominent components of photoaging in darker complected individuals . The blotchy pigment is probably due in part to uneven distribution of melanocytes and marked variation in their pigment production . Solar lentigines are well circumscribed hyperpigmented macules or patches commonly seen in the heaviest areas of exposure in sun damaged individuals. A variant of the irregularly pigmented common solar lentigo are large, uniformly pigmented macules and patches which are characteristic of areas of acute erythemal exposure and can be seen in young adults and children as well as older individuals .
Animal studies suggest that the UVA portion of sunlight probably contributes substantially to sagging and wrinkling [67, 76]. Chronic UV exposure in humans leads eventually to loss of skin elasticity, fragility and hemorrhage of blood vessels, a condition clinically termed senile purpura [77, 78]. Interestingly, animal studies suggest that lower intensity exposures can actually enhance the wrinking effect of UV , suggesting a greater role for cumulative damage for this particular UV effect.
Ultraviolet exposure causes a number of adverse consequences for the immune system including suppression of cutaneous immune responsiveness and immunologic unresponsiveness to cutaneous tumors [80, 81]. Local mechanisms for these effects include depletion of resident Langerhans, Thy1+ and dendritic epidermal T cell populations [82-85]. Systemic mechanisms include production of suppressor T-cells [84, 86] and release of soluble immunosuppressive factors such as cis-urocanic acid, tumor necrosis factor-alpha [87, 88], interleukin-1, prostaglandins , and interleukin-10 .
Ultraviolet and Melanoma Formation
A number of epidemiologic studies in the last several decades indicate that sunlight is a major etiologic factor in melanoma . Several studies in a variety of European countries have shown an inverse relationship between increasing latitude and melanoma mortality [92-95]. In other words, as latitude decreases from the pole to the equator, the death rate from melanoma increases. Similar findings were noted in North America by Elwood et al., who found that a decrease in latitude of 2ºwas associated with a 10% increase in the death rate from melanoma . The most likely explanation from these findings is that melanoma mortality (and incidence) varies with amount of UV energy reaching the earth's surface, which is a function of latitude [97-99].
In addition to this geographic evidence, melanoma is primarily a disease of lightly complected individuals, a fact which is probably due to the known UV-protective effects of melanin. In the Indian sub-continent, populated predominantly by individuals of skin type 4 or 5, the age-standardized incidence of melanoma has been estimated at around 0.2 per 100,000. In Australia by contrast, the incidence in the predominately skin type 1-3 populace living at roughly the same latitude has been estimated at around 30 per 100,000, a difference in incidence of over two orders of magnitude . In Los Angeles, rates in Japanese and Chinese descended Americans (predominately type 4 skin) were estimated at less than 1 per 100,000, while the rate in a lighter complected Caucasian group was 11-12 per 100,000 .
Studies done in melanoma-predisposed individuals suggests a role for sun protection in the management of the problem. Recent evidence from melanoma prone families demonstrate that sunlight is linked to expression of the disease in genetically susceptible individuals . The development of numerous benign nevi, one of the known risk factors for melanoma, is now known to be connected to personal sun exposure, especially multiple sunburns [103, 104]. Similarly, atypical nevi, which also increase melanoma risk, have been linked to sun exposure, particularly intense sun exposure [104-107]. Finally, the anatomic distribution of melanoma lesions suggests that sun exposure plays a role in their formation. In men, melanoma lesions are seen predominately on the back and face, whereas in women, the incidence on the leg is substantial . As expected, the incidence on covered sites of the body is much lower .
Melanoma Action Spectrum in Animals. Animal models have contributed significantly to understanding the carcinogenic effects of UV radiation. In vitro and in vivo data in experimental animals suggest that UVB is the major action spectrum for melanoma. UVB has been shown to transform melanocytes from SV40 transgenic mice . In the South American opossum model, melanomas are induced by UVB [20-22]. Data from the Xiphophorus fish model of melanoma also indicates an action spectrum peak for melanoma in the UVB range . Although UVB appears to be the major cause of melanoma in this model, wavelengths longer than 304 can contribute significantly to melanoma formation in ultra-sensitive strains of the fish .
Melanoma Action Spectrum in Humans. In a recent review published by the World Health Organization, fifteen of seventeen studies of melanoma in which sunburn was recorded showed a statistically significant, moderately to strongly positive association of melanoma with a history of sunburn . Since UVB is the major wavelength in sunlight that causes sunburn, these studies tend to substantiate the view that UVB is the major action spectrum of melanoma formation in humans .
Studies of sunlamp users provide the only direct data relating to the wavelength of melanoma causation in humans. Two recent studies found both an association between melanoma risk and sunlamp use and an excess risk associated with individuals who used the devices prior to 1980 compared with sunlamp use subsequent to 1980 [114-115]. The hypothesis advanced to explain this finding was that an excess of UVB exposure from earlier models of sunlamps created a greater incidence of melanoma among these users compared with later sunlamp users who were exposed to a more uniform UVA spectral output [6, 114, 115].
Ultraviolet and Non-Melanoma Skin Cancer
The UVB wavelength range is the most efficient at producing squamous tumors in experimental animals, i.e., at much lower fluences than UVC or UVA radiation . Studies in experimental mice suggest a peak action spectrum around 300 nm, similar to that seen in the fish melanoma model [111, 116]. Perhaps the best estimate of the action spectrum for squamous cell carcinomas was made by de Gruijl et al., who pooled animal data from a number of experiments. These investigators found a peak action spectrum of 293 nm with a substantial tail into the short UVA region (315-340) .
The simplest strategy for protection from the harmful effects of sunlight is avoidance. Studies of ultraviolet intensity have shown that about 30% of the total daily UV flux hits the earth between 11 AM and 1 PM, so that if possible, activities should be planned to avoid this peak exposure time . A useful rule of thumb is that if your shadow is shorter than you, the risk of sunburn is substantial .
Since 1994, the National Weather Service (NWS) has implemented the UV index, an experimental project to predict the burning potential of daily UV exposure based on the maximum expected ultraviolet flux expected for the forcast region. The index is reported as a number on a scale of 0-15 with 15 being the maximum burning potential. The Index developed by the NWS, with the support of the U.S. Environmental Protection Agency (EPA) and the Centers for Disease Control and Prevention (CDC). The EPA is responsible for public education and outreach, with assistance from the CDC. Access to this information is available on the World Wide Web through the EPA's Ozone Depletion Home Page (http://www.epa.gov/docs/ozone/index.html), and the National Oceanic Administration (http://www.noaa.gov/uvb/appen.html). The value of the index is probably best illustrated by how it affects the estimated time to sunburn for various skin types (see Table 1). This allows an estimate of the degree of risk of UV exposure on a given day in a given region that may help in planning outdoor activities and urgency of adequate sun protection measures.
Another possibility that should not be overlooked is protective clothing. Clothing is generally a good UV blocker, although lighter fabrics that are desirable because they are cooler may not have as great a protective value as heavier fabrics such as denim, which is generally the most protective. The sun protection value of fabric is more a function of the hole size of the fabric mesh than the particular fabric type [119-121].
Jevtic showed that a cotton/polyester T-shirt has a sun protection factor (SPF--see below for a definition) value of around 15, although the SPF value decreased when the fabric was wet . Interestingly, a cotton T-shirt may actually increase in SPF value when it is washed a few times due to shrinkage in the hole size of the fabric mesh .
A useful rule of thumb is to hold a shirt up to a strong light source such as a light bulb. If you can see images through it, it probably has an SPF value less than 15. If light gets through, but you can't really see through it, it probably has a SPF value somewhere between 15 and 50. If it completely blocks all light, it probably has an SPF value greater than 50 (e.g. heavy cotton denim).
Hats are of great value, since they cover the head and neck which gets almost continual sun exposure, even in winter. Retrospective study of multiple skin cancers suggest that hats may help to decrease the risk . The best ones are the ones with a wide (at least 2-3 inch) brim that goes all the way around. Diffey showed by means of film badge exposure measurments that hats with a 3 inch (7.5 cm) brim afford substantially better UV protection . The worst ones by contrast are the baseball style caps that have the transparent mesh backs for comfort. These are better than nothing, but obviously don't provide coverage for the ears, neck and vertex of the scalp.
A tan is essentially the skin's way of increasing its defense against the onslaught of damaging UV. Tanning protects against sun damage principally by increasing the melanin content of the epidermis.
While it is true that the greater the skin pigmention the better as far as sun protection goes, it does not necessarily follow that intentional tanning specifically to achieve an increase in protective pigmentation is the best sun protection strategy (see below for a discussion of tanning through sunscreens). Recent evidence suggests that tanning only occurs after DNA damage has already occurred . Essentially, DNA damage is the trigger for the tanning response, meaning that tanning doesn't begin until you have done at least some damage, leading to the conclusion that there really is no safe level of sun exposure. It should also be noted that tanning with high intensity UVA (tanning parlors) does not lead to as great a protective effect as tanning with natural sunlight [23, 126, 127].
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