Estrogen receptor-beta signaling protects epidermal cytokine expression and immune function from UVB-induced impairment in mice.

A previous study in the hairless mouse, in which the photoimmune protective properties of a topical phytoestrogen or 17-beta-estradiol were abrogated by the estrogen receptor antagonist ICI 182,780, revealed that estrogen receptor (Er) signaling is involved in the regulation of the suppression of immune function by UVB (290-320 nm) radiation. Here we identify the expression of Er-beta but not Er-alpha mRNA in hairless mouse skin, whereas Er-alpha and Er-beta mRNA were present in normal haired mouse skin. This suggests that the non-classical estrogen target Er-beta is involved in the photoimmune modulation, and is consistent with Er-alpha being more closely associated with hair growth control, as indicated by other studies. In mice with a null mutation for Er-beta, there was a significant exacerbation of the solar simulated UV (290-400 nm)-induced suppression of contact hypersensitivity. Immunohistochemical analysis revealed that the Er-beta deficiency inhibited the normally immunoprotective upregulation by the UVA (320-400 nm) waveband of the epidermal expression of the cytokines IFN-gamma and IL-12. Er-beta deficiency also significantly increased the UVB-induced expression of the immunosuppressive cytokine IL-10. Thus Er signalling via the Er-beta is evidently a major regulator of the UVA and UVB waveband interactions that determine the skin's immune functional status, and achieves this by normalization of the cutaneous cytokine array in the UV-irradiated skin.     

Ultraviolet irradiation induces the accumulation of chondroitin sulfate, but not other glycosaminoglycans, in human skin

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV.     

Aromatic amino acid oxidation products as antioxidants

The accumulation of UV photolysis products of amino acids tyrosine and tryptophan, which possess antioxidant activity, has been studied by the method of luminol-dependent chemiluminescence. The amount of antioxidant products was judged by the value of the total antioxidant potential of a UV-irradiated solution, the measure of which was the distance between the peaks of the chemiluminescence curve in the system 2,2′-azo-bis(2-amidinopropane) hydrochloride + luminol with a UV-irradiated and an unirradiated sample (induction period, τ _i ). Simultaneously, the absorption and fluorescence spectra of unirradiared and UV-irradiated amino acid solutions were recorded. It was shown that exposure of a tryptophan solution to radiation led to accumulation of a fluorescent product N-formyl kynurenine (λ_em = 325 nm, λ_max = 440 nm), and the curve of its accumulation was similar to the growth of antioxidant potential. When a tyrosine solution was irradiated, the main fluorescent product was dityrosine (λ_em = 310 nm, λ_max = 415 nm). Nevertheless, the dose dependences of the formation of dityrosine and the total antioxidant potential were completely different. It was found that another product of tyrosine UV photolysis, dihydroxyphenylalanine, possessed pronounced antioxidant activity. It was concluded that the main antioxidant produced under UV irradiation of tryptophan is formyl kynurenine, and under irradiation of tyrosine it is dihydroxyphenylalanine.     

Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol.

Over 1 million new cases of ultraviolet radiation-induced non-melanoma skin cancers (NMSC) per year now occur in the USA and the incidence of these diseases continues to increase. New preventative strategies are required. The hypothesis tested was that dietary administration of the putative cancer chemopreventatives sodium-copper-chlorophyllin (Chlor) or indole-3-carbinol (I3C) would inhibit UV-induced skin carcinogenesis in the Crl:SKH1:hr-BR hairless mouse. Groups of 20 mice were pre-fed isocaloric/isonutritive 20% corn-oil AIN-76a based diets that contained either Chlor (1.52 g%), I3C (5.08 g%) or no chemopreventative (control) for 2 weeks followed by exposure of their dorsal skin to a 10 week incremental, sub-erythemal, carcinogenic simulated solar UV exposure regime. Feeding was continued for the duration of the experiment. Matched non-UV exposed dietary groups were also included in the experimental design. The diets had no significant (p > 0.05) effect on body weight, feed consumption, cutaneous methanol-extractable UV photoprotective substances or on cutaneous UV-reflective characteristics. By day 180, UV-irradiated mice fed the Chlor had a significantly (p < 0.05) higher tumor multiplicity (33.6 +/- 4.72; mean +/- SEM) than UV-irradiated control animals (22.8 +/- 4.25). UV-irradiated mice fed I3C had a significantly (p < 0.001) lower tumor multiplicity (13.0 +/- 2.42) than that of both the UV-irradiated control and UV-irradiated Chlor-fed mice. The Chlor or I3C diets did not significantly (p > 0.05) affect UV-induced systemic suppression of contact hypersensitivity responses. These results demonstrate augmentation of the UV-induced cutaneous carcinogenic process by dietary chlorophyllin and protection from this carcinogenic process by indole-3-carbinol via mechanisms that do not involve changes in skin optical properties, modulation of photoimmunosuppression or caloric/nutrient effects.     

Photoimmune protective effect of the phytoestrogenic isoflavonoid equol is partially due to its antioxidant activities

Topical application of lotions containing the phytoestrogenic isoflavonoid equol have been reported to protect mice against UV radiation-induced inflammation, immune suppression and photocarcinogenesis. The photoimmune protective property was shown to depend on equol's activation of oestrogen receptor signalling in the skin. However, isoflavones are also recognised for their antioxidant properties in biological systems. As endogenous cutaneous antioxidant enzymes including the inducible stress protein haem oxygenase (HO)-1, have photoprotective efficacy, this study in the Skh:hr-1 hairless mouse seeks evidence for an antioxidant role for equol in contributing to its photoimmune protection. Oxidative stress has been measured as UVA-induced lipid peroxidation in the mouse skin, and was dose-dependently inhibited by topical equol. Inhibition of the UVA (320-400 nm)-inducible HO activity significantly reduced the level of equol protection against lipid peroxidation, thereby attributing a component of equol's lipid protection capacity to this stress enzyme. It was consistent that topical equol enhanced the level of HO induction by UVA irradiation in both skin and liver. Subsequently, the dose-dependent protection by topical equol lotions against solar simulated UV radiation induced immunosuppression, measured by the contact hypersensitivity reaction, was found also to be partially reduced by the inhibition of HO activity. Therefore, in addition to the activation by equol of oestrogenic signalling pathways for photoprotection, this isoflavonoid also provides UV-protective antioxidant effects that depend partially on HO-1 induction.     

Gender differences in UV-induced inflammation and immunosuppression in mice reveal male unresponsiveness to UVA radiation

Immunosuppression attributed mainly to the UVB (290-320 nm) waveband is a prerequisite for skin cancer development in mice and humans. The contribution of UVA (320-400 nm) is controversial, but in mice UVA irradiation has been found to antagonise immunosuppression by UVB. In other studies of photoimmune regulation, protection mediated via oestrogen receptor-β signalling was identified as a normal endogenous defence in mice, and was shown to depend on UVA irradiation. A gender bias in photoimmune responsiveness was thus suggested, and is tested in this study by comparing the UV-induced inflammatory and immune responses in male and female hairless mice. We report that male mice, which show greater skin thickness than females, developed a less intense but slower resolving sunburn inflammatory oedema, correlated with reduced epidermal expression of pro-inflammatory IL-6 than females following solar simulated UV (SSUV, 290-400 nm) exposure. On the other hand, the contact hypersensitivity reaction (CHS) was more severely suppressed by SSUV in males, correlated with increased epidermal expression of immunosuppressive IL-10. Exposure to the UVB waveband alone, or to cis-urocanic acid, suppressed CHS equally in males and females. However, whereas UVA irradiation induced immunoprotection against either UVB or cis-urocanic acid in females, this protection was significantly reduced or abrogated in males. The results indicate that males are compromised by a relative unresponsiveness to the photoimmune protective effects of UVA, alone or as a component of SSUV. This could explain the known gender bias in skin cancer development in both mice and humans.     

Antioxidants as aromatic amino acid oxidation products

The accumulation of UV photolysis products of amino acids tyrosine and tryptophan, which possess an antioxidant activity, has been studied by the method of luminol-activated chemiluminescence. The amount of antioxidant products was judged by the value of the total antioxidant potential of a UV-irradiated solution, the measure of which was the distance between the peaks of the chemiluminescence curve in the system 2,2'-azo-bis(2-amidinopropane)hydrochloride + luminol in a UV-irradiated and an unirradiated samples (induction period, tau(i)). Simultaneously, the absorption and fluorescence spectra of unirradiared and UV-irradiated amino acid solutions were recorded. It was shown that, upon the exposure of a tryptophan solution to radiation, the accumulation of the fluorescent product N-formyl kynurenine (lambda(em) = 325 nm, lambda(max) = 440 nm) occures, and the curve of its accumulation was similar to the curve of growth of tau(i) photoproducts produced during UV-radiation. When a tyrosine solution was irradiated, the main fluorescent product was dityrosine (lambda(em) = 310 nm, lambda(max) = 415 nm). Nevertheless, the dose dependencies of the formation of dityrosine, and the total antioxidant potential (tau(i)) were completely different. It was found that another product of tyrosine UV-photolysis, dioxyphenylalanine, possessed a pronounced antioxidant activity. It was concluded that the main antioxidants produced under UV-irradiation of tryptophan is formyl kynurenine, and under the irradiation of tyrosine, dioxyphenylalanine.     

Some acute effects of monochromatic ultraviolet B irradiation on mouse epidermis measured by the tetrazolium-reduction test and determination of DT-diaphorase activity, with reference to carcinogenesis

Some acute epidermal effects of monochromatic ultraviolet B (UVB) irradiation on hairless mouse skin were measured by the tetrazolium test (TZT), and by determining the DT-diaphorase activity in epidermal cells. Dose response and time course studies were carried out after UVB irradiation at 280, 290, 297 and 302 nm. Appropriate UV doses at all the wavelengths increased the cellular deposition of formazan (TZT). At higher doses the epidermal cells became too injured to react. Wavelengths at 280 and 290 nm seemed more injurious than those at 297 and 302 nm. There was, however, no increase in DT-diaphorase activity after UVB irradiation. This indicates that the increased formazan deposition (TZT) after UVB is more likely to be caused mainly by membrane effects. Detoxification mechanisms which activate DT-diaphorase, as often seen after cellular contact with chemical carcinogens, are not involved.     

A fingerprinting method for chondroitin/dermatan sulfate and hyaluronan oligosaccharides

A previously published method for the analysis of glycosaminoglycan disaccharides by high pH anion exchange chromatography (Midura,R.J., Salustri,A., Calabro,A., Yanagishita,M. and Hascall,V.C. (1994), Glycobiology,4, 333-342) has been modified and calibrated for chondroitin and dermatan sulfate oligosaccharides up to hexasaccharide in size and hyaluronan oligosaccharides up to hexadecasaccharide. For hyaluronan oligosaccharides chain length controls elution position; however, for chondroitin and dermatan sulfate oligosaccharides elution times primarily depend upon the level of sulfation, although chain length and hence charge density plays a role. The sulfation position of GalNAc residues within an oligosaccharide is also important in determining its elution position. Compared to 4-sulfation a reducing terminal 6-sulfate retards elution; however, when present on an internal GalNAc residue it is the 4-sulfate containing oligosaccharide which elutes later. These effects allow discrimination between oligosaccharides differing only in the position of GalNAc sulfation. Using this simple methodology, a Dionex CarboPac PA-1 column with NaOH/NaCl eluents and detection by absorbance at 232 nm, a quantitative analytical fingerprint of a chondroitin/dermatan sulfate chain may be obtained, allowing a determination of the abundance of chondroitin sulfate, dermatan sulfate, and hyaluronan along with an analysis of structural features with a linear response to approximately 0.1 nmol. The method may readily be calibrated using either commercial disaccharides or the di- and tetrasaccharide products of a limit digest of commercial chondroitin sulfate by chondroitin ABC endolyase. Commercially available and freshly prepared shark, whale, bovine, and human cartilage chondroitin sulfates have been examined by this methodology and we have confirmed that freshly isolated shark cartilage CS contains significant amounts of the biologically important GlcA2Sbeta(1-3)GalNAc6S structure.     

Solar Ultraviolet Irradiation Induces Decorin Degradation in Human Skin Likely via Neutrophil Elastase

Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils. Type I collagen is the most abundant protein in skin and constitutes the majority of skin connective tissue (dermis). Degradation of collagen fibrils impairs the structure and function of skin that characterize skin aging. Decorin is the predominant proteoglycan in human dermis. In model systems, decorin binds to and protects type I collagen fibrils from proteolytic degradation by enzymes such as MMP-1. Little is known regarding alterations of decorin in response to UV irradiation. We found that solar-simulated UV irradiation of human skin in vivo stimulated substantial decorin degradation, with kinetics similar to infiltration of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN cells degraded decorin in vitro. A highly selective inhibitor of neutrophil elastase blocked decorin breakdown by proteases released from PMN cells. Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated fragments with similar molecular weights as those resulting from protease activity released from PMN cells, and as observed in UV-irradiated human skin. Cleavage of decorin by neutrophil elastase significantly augmented fragmentation of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN cell proteases, especially neutrophil elastase, degrade decorin, and this degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These data identify decorin degradation and neutrophil elastase as potential therapeutic targets for mitigating sun exposure-induced collagen fibril degradation in human skin.     

Effectivity of bacterial repair systems in near UV radiation-induced damage

Inactivation of seven strains derived fromEscherichia coli B differing in their capacity to repair damage to their DNA (exc, pol, rec) after irradiation with far (254 nm) and middle and near (300 to 380 and 320–400 nm) UV light was investigated. The same bacterial strains were also used as hosts for the UV-irradiated pliage T7. The damage induced in bacteria and the phage by the near UV radiation was repaired only to a lesser extent by the investigated repair mechanisms or was not repaired at all.     

Dielectric investigations of murine cancer cells

We have emphasised electrical polarization mechanisms that are responsible for biomacromolecular rearrangements and biochemical processes in skin cells during carcinogenesis developed by ultraviolet irradiation. At 1591.5 Hz, the dielectric permittivity values of the skin of hairless intact mice, considered as a model susceptible to skin cancer induced by UV irradiation, were measured. The dielectric responses of cancer-induced cells sensitively vary when compared with responses of mechanically or chemically (tumor activators) treated skin cells, despite that histological examinations are not deterministic. Such differences, if generally existing between tumor and normal or noncarcinogenic-treated skins, could be used to advantage in clinical application of electromagnetic fields.     

Phototaxis in a dinoflagellate: Action spectra as evidence for a two-pigment system

Summary Action spectra were determined in the UV region of the spectrum for the first phase of the phototactic response (stop response) and for the phytochrome pigment associated with this response in the dinoflagellate Gyrodinium dorsum Kofoid. Differences between these action spectra indicate the participation of two pigments in phototaxis. Following R (620 nm) irradiation of the phytochrome, the stop response maxima occur at 470 and 280-nm; after FR irradiation they shift to 490 and 300–310 nm. These maxima suggest that the photoreceptor pigment for phototaxis is a carotenoprotein. The action spectrum shift following the different phytochrome conversions may represent a trans to cis isomer change by the carotenoid. The absorption maximum of P_R in the UV appears to be at 320 nm, which is consistent with the shift of the R absorption maximum to shorter wavelengths (620 nm) as compared to higher plants. The P_FR absorption maximum appears as a broad band between 360 and 390 nm. Comparison of P_R to P_FR conversions by different intensities of 620-nm and 320-nm light indicates that at lower intensities the logarithm of the threshold for the stop response is inversely proportional to the logarithm of the intensity of the sensitizing light. The ratio of response activation by R and UV light is about 4:1.Abbreviations FR far-red - R red - P_FR far-red-absorbing form of phytochrome - P_R red-absorbing form of phytochrome - UV ultraviolet     

Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis.

The induction of skin cancers in mice by chronic UV irradiation is accompanied by a decrease in the numbers of Ia+ and Thy-1+ dendritic cells in the epidermis early in the course of UV irradiation. Subsequently, the number of Ia+ cells, but not Thy-1+ cells, increases until the time of tumor development. To assess the functional significance of these changes in cutaneous immune cells, and to help define the role these cells may play in immune surveillance against skin cancers, we tested the afferent immunologic capability of the skin during the development of UV-B radiation-induced skin cancers. Afferent immune function was measured by testing the Ag-presenting capacity of draining lymph node (DLN) cells from mice sensitized epicutaneously with dinitrofluorobenzene. A reduced contact hypersensitivity response was induced in mice immunized with DLN cells from UV-irradiated mice that had been sensitized with hapten on UV-irradiated skin. This decreased reactivity was present during the entire latent period of tumor development. However, in tumor-bearing mice, the DLN cells from UV-irradiated, sensitized animals exhibited normal Ag-presenting activity. DLN cells from UV-irradiated mice sensitized on ventral, unirradiated skin exhibited normal Ag-presenting activity. The lowest amount of Ag-presenting activity in the draining lymph nodes of UV-irradiated mice correlated temporally with the lowest number of Ia+, adenosine triphosphatase+ dendritic epidermal cells in the UV-irradiated skin. At least during the early part of the tumor latent period, an increase in the number of these cells was paralleled by an increase in the Ag-presenting activity of the DLN cells. In contrast, the number of Thy-1+ dendritic epidermal cells in UV-irradiated skin did not correlate with the Ag-presenting activity. Thus, the decrease in the number of identifiable epidermal Langerhans cells early in the course of chronic UV irradiation correlated with a decrease in Ag-presenting activity after sensitization through the UV-irradiated skin. These studies demonstrate that the afferent arm of the cutaneous immune response is impaired in the site of tumor development throughout the latent period of UV carcinogenesis.     

Photoinactivation of lymphohemopoietic cells: studies in transfusion medicine and bone marrow transplantation.

Ultraviolet (UV) irradiation affects eukaryotic cells in numerous ways. Exposure of blood transfusion products to UVC (200-280 nm) or UVB (280-320 nm) reduces or abrogates their immunogenicity and thereby prevents allosensitization and transfusion refractoriness in several models. Although the exact mechanism is not known, in vitro studies suggest that UV exposure results in a loss of class II histocompatibility antigens from the cell surface, alterations of calcium homeostasis, and a lack of interaction between antigen presenting and responding cells. In the UVB and UVA (320-400 nm) range, lymphocytes appear to be more sensitive than hemopoietic cells. In murine transplant models, UVB irradiation of spleen and marrow cells can be used to prevent the development of graft-versus-host disease while allowing for complete hemopoietic reconstitution. Furthermore, in clinical marrow transplantation, pilot studies of UVA in conjunction with psoralen administration have yielded encouraging results in patients with steroid refractory graft-versus-host disease of the skin. Thus, UV irradiation provides an interesting tool to study cell/cell and donor/host interactions and may have some applications in transfusion medicine and bone marrow transplantation.     

Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice

Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4-5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating L-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5-16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34±0.32), arginine (Arg, 1.66±0.39), glutamine (Gln, 1.75±0.60), and proline (Pro, 1.48±0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56±0.30). However, essential amino acids mixtures (BCAA+Arg+Gln, BCAA+Gln, and BCAA+Pro) significantly increased the FSR (2.07±0.58, 2.04±0.54, 2.01±0.50 and 2.07±0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation.     

Anti-aging and anti-inflammation effects of natural mineral extract on skin keratinocytes

In this study, we investigated the effects of a natural mineral extract on damaged skin keratinocytes. We have focused on the possible effects of the natural mineral extract on UV-irradiated normal human skin keratinocytes. Human keratinocytes were UV-irradiated and were treated with 0.1, 1.0, or 10% of natural mineral extract. Study controls included non-UV-irradiated cells, UV-irradiated cells (no extract), and UV-irradiated cells treated with 25 nM ascorbic acid. Cell viability following UV irradiation was significantly higher in the groups treated with the natural mineral extract at doses of 0.1, 1.0, and 10% than in the control group with UV irradiation only. The UV-irradiated cells demonstrated increased secretion of laminin relative to non-irradiated controls. We found that treating these UV-irradiated keratinocytes with natural mineral extract reduced vacuole size and number, and it dose-dependently increased laminin secretion and reduced IL-2 synthesis. Also, MMP-1 and MMP-2 activity were significantly less in cells treated with natural mineral extract than in UV-irradiated controls. The UV irradiation reduced MMP-1 levels to 45±5 ng/mL from 130±5 ng/mL. In addition, MMP-2 production in keratinocytes was significantly reduced by 11±1 ng/mL compared to the UV-irradiation control. In conclusion, the results of this work suggest that natural mineral extract has effects on keratinocytes damaged by UV exposure.     

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.

Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115-0.23 J/cm2 results after 24-48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-alpha-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40-55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel non-invasive technique not previously reported for this purpose--magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p less than 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p less than 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p less than 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-alpha-tocopherol which is stable to autooxidation.