The use of sunscreens in preventing skin cancer.
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Biomedical subjects
Publications and source records attributed to R M Sayre.
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To determine an action spectrum for ultraviolet (UV)-induced elastosis, four groups of 24 albino hairless mice each were exposed to four different spectra emitted by a xenon arc solar simulator fitted with cut-off filters (Schott WG 320, 335, 345, and 360). These filters progressively removed more of the shorter wavelengths until, in the final spectrum, only long wavelength UVA (greater than 335 nm) remained. Exposures continued up to 62 weeks. A fifth group of mice served as controls. Skin biopsies were taken at pre-determined dose points and were processed for light microscopy. Elastosis was quantified by computerized image analysis, yielding dose-response curves for each spectrum. The total energy required for a 50% increase in elastic tissue compared to controls was determined graphically for each spectrum. These were: WG 320, 65 J/cm2; WG 335, 865 J/cm2; WG 345, 1230 J/cm2; and WG 360, 2000 J/cm2. Our results were tested against published action spectra for erythema, photocarcinogenesis and elastosis. The erythema spectrum was the most predictive for elastosis except that the longer UVA wavelengths were less effective for elastosis than for erythema. Solar simulating radiation (WG 320 filter) with its UVB component was the most effective in inducing elastosis. Full spectrum UVA (WG 345) required 20 times more energy while long wavelength UVA (WG 360) required 30 times more energy to induce equivalent elastosis.
A number of factors may alter the efficacy of a sunscreen product being tested. Notably among these are (1) the source of ultraviolet (UV) radiation, (2) the filtration of the UV radiation source, (3) such environmental factors as swimming or sweating (4) and/or the amount of product applied. This is the first report in which the technique of product application itself is examined. We find that the act of rubbing the product into the skin appears also to remove product from the skin. In our study, different techniques of product application produced a 25% deviation in product sun protection factor. The variables associated with the application of sunscreening products are discussed.
Although the UVB portion of the electromagnetic spectrum (290 to 320 nm) is responsible for most of the harmful effects of sunlight on the skin, wavelengths in the UVA region also contribute to photodamage. A simple and rapid clinical test, the sun protection factor determination, is available to assess the sunburn protective effect of a sunscreen, primarily a UVB effect. However, no practical test has been proposed to measure a sunscreen's UVA protection. We described a method for the calculation of UVA protection in normal subjects. The determination of UVA protection involves three steps: (1) the UV absorbance spectrum of the sunscreen on skin is determined spectrophotometrically; (2) a convolution spectrum is calculated by multiplying the solar spectrum with the Commission Internationale de l'Eclairage UV Hazard Spectrum; and (3) the sunscreen transmission spectrum is then incorporated into the convolution spectrum to obtain the UVA effectiveness ratio, which can be expressed as the UVA protection percentage. Because the UVA protection percentage value is based both on normal erythemic risk and on standard sunlight, the protection for any product can be easily measured. The procedure is simple, and values generated can be reproduced in other laboratories.
In evaluating sunscreen efficacy, spectral distribution of the irradiation sources can influence the sun protection factor (SPF). The purpose of this investigation was to examine the uniformity of ultraviolet (UV) spectral irradiance of solar simulators used in various SPF testing laboratories, compare them with natural sunlight UV radiation (UVR), and recommend performance limits to ensure that the variability of radiation sources in the UVB region minimally affects SPF estimates. The critical portion of the solar erythemogenic spectrum was identified as the UVB portion, defined as the region between 280 and 320 nm. The spectral irradiance of 26 solar simulators and other UV sources was measured and compared with a summer noon solar spectrum measured in Albuquerque, NM. Proposed spectral limits were developed as a 6-nm "acceptance band" centered on this standard spectrum normalized at 320 nm. The results indicated that the xenon-arc solar simulators currently used in the United States in testing sunscreens either meet the proposed standard solar spectrum or can be readily modified with available UV filters to meet this standard. The devices that have spectral characteristics not resembling sunlight fail to meet the proposed standard and should not be used for sunscreen SPF testing.
Reciprocity for sunscreen solar protection factors (SPFs) and for delayed erythema was examined using a solar simulator equipped with neutral density filters to vary the beam intensity. Similar SPFs were obtained over a 15-fold intensity difference, using a sunscreen with a low (SPF-4) and a high (SPF-15) protection factor. Reciprocity was also observed for delayed erythema in unprotected skin.
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Dopa phosphates, a new class of compounds, contain phosphate-ester linkages at the 3- and/or 4- positions of the phenylalanine ring of L-dopa. Dopa phosphates have been shown to increase pigment production in the epidermis of hairless mice. Groups of Skh-2 pigmented hairless mice were treated topically with various concentrations of dopa phosphates daily for five weeks. Half of each group received suberythemal UVB radiation three times weekly for four weeks from a bank of filtered FS20 lamps. UVB and dopa phosphates alone each caused a modest increase in epidermal pigmentation. However, treatment of mice with dopa phosphates plus UVB radiation resulted in a marked increase in pigmentation, greater than with either treatment alone. The optimal concentration of dopa phosphates was 0.01% (100 micrograms/ml Tris-glycerol buffer) whether or not they were applied in conjunction with UVB radiation. Histological analyses revealed that dopa phosphates and UVB radiation each caused an increase in the number of pigmented melanocytes in the epidermis. Control groups treated with Tris-glycerol buffer alone, or buffer containing L-phenylalanine or L-dopa showed no significant changes in pigmentation. Our results indicate that dopa phosphates stimulate the production of melanin and affect the development and distribution of melanocytes in the skin of Skh-2 mice. By these criteria, dopa phosphates and UVB act in a similar manner to increase melanin content in the skin. The processes may be related to those recently observed in cultured mouse melanoma cells where dopa phosphates are incorporated into melanin, presumably following enzymatic hydrolysis by cellular phosphatases with the resultant production of L-dopa and inorganic phosphate.
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Mouse skin, unlike human skin, does not contain active epidermal melanocytes, with the exception of the ear and tail skin in some pigmented strains. We have investigated enhancement of pigmentation in inbred C3H- mice using tail skin as a model for testing the effects of phosphorylated DOPA (DP) and ultraviolet radiation. Mice were restrained by cage dividers and treated with various doses of DP in dimethylsulphoxide (DMSO) or DMSO alone with or without the addition of UV radiation. Each tail served as its own control since only the dorsal surface was treated and irradiated. Pigmentation was graded blindly on histologic sections stained with Fontana-Masson. UV radiation caused a marked increase in epidermal and dermal pigmentation and this was enhanced in a dose-dependent manner by DP. However, there was minimal effect from DP alone.
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Immediate pigment darkening (IPD) was recorded in over 1,300 volunteers participating in routine sun protection factor (SPF) testing. Medical history obtained included skin type, hair color, eye color, sunburn sensitivity, tanning ability, and current medications. The presence of IPD and the energy needed to produce it were recorded immediately following exposure to a filtered 2500 W xenon are solar simulator. Minimal erythemal dose (MED) values were recorded 16-24 hours post-exposure. The average MED was lowest for skin type I and highest for skin type IV. The IPD dose was also lowest for skin type I and highest for skin type IV. However, the average IPD dose was greater than the MED for skin type I and lower than the MED for skin type IV. For skin types II and III, the average IPD dose and MED were almost equivalent. For skin type I, 64% required equivalent or greater energy to produce IPD than their MED, and 30% showed no IPD at energy levels sufficient to produce erythema, whereas all skin type IV's had a measurable IPD response. For volunteers of skin type II and III showing no measurable IPD, the predominant eye color was blue or green (74%). Sunscreen usage altered the IPD response for all 4 skin types.
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Minimal erythema doses (MEDs) of individuals with different skin types were compared. Each skin type was shown to be statistically different from each other skin type in terms of sunburn sensitivity. Individuals of each skin type who primarily stayed indoors were compared with those who attempted to be outdoors. In the winter there was no difference between the sunburn sensitivity (MEDs) of these groups. During the summer, those who went outdoors were more resistant to sunburn than those who stayed indoors. In effect, acclimatization makes an individual respond to sunlight like a less sensitive skin type. However, acclimatization appears transitory, and benefits can be lost within a month or two.
Groups of skh-1 (albino) and Skh-2 (pigmented) hairless mice were irradiated for 125 hr using a modified GE F8T5-BL black light with and without a 3-mm plate glass filter to remove light below 320 nm. The epidermis was examined by forward scattering and by histological section postirradiation at 48 hr, 96 hr, 9 days, and 23 days. Changes in the epidermis of all animals were compared to control groups. Although no differences were seen between Skh-1 and Skh-2 mice, both the magnitude and shape of the forward scattering absorption curves were changed by the irradiation used. In both strains, differences which were detected at 48 hr postirradiation had returned to normal visually by 23 days, with no augmented pigmentation occurring in Skh-2 animals. At 23 days postirradiation, however, residual optical alterations were observed. This phenomenon, detected optically, may be skin acclimatization.
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The photoprotective role of melanin was evaluated by comparing the transmission of ultraviolet (UV) radiation through skin samples of blacks and Caucasians, using both biologic and spectroscopic techniques. UVA transmission was measured using fluoranthene, which causes a phototoxic response to UVA wavelength. UVB was measured by monitoring erythema produced by either a 150-watt xenon arc or FS-20 sunlamps. It was found that on the average, five times as much ultraviolet light (UVB and UVA) reaches the upper dermis of Caucasians as reaches that of blacks. Differences in transmission between the stratum corneum of blacks and of Caucasians were far less striking. The main site of UV filtration in Caucasians is the stratum corneum, whereas in blacks it is the malpighian layers. Melanin acts as a neutral density filter, reducing all wavelengths of light equally. The superior photoprotection of black epidermis is due not only to increased melanin content but also to other factors related to packaging and distribution of melanosomes. Not only are these data consistent with epidemiologic evidence, but they also may indicate why blacks are less disposed to phototoxic drug responses as well as less susceptible to acute and chronic actinic damage.