UVA filters in sun-protection products: regulatory and biological aspects.

This review of published in vitro and in vivo studies concerning the biological effects of ultraviolet A (UVA; 320-400 nm) radiation illustrates the evidence for combining UVA and UVB filters in sun-protection products. These data have led to the development of new sunscreens as well as methods to evaluate their efficacy. After listing the UVA filters available and briefly noting the requirements for a high SPF, broad-spectrum sunscreen, the methods for evaluating the level of UVA protection will be described. This article also summarizes several studies looking at the prevention of erythema, pigmentation, DNA damage, photoimmunosuppression, photoaging and photodermatoses. These data demonstrate in vitro and in vivo that only well-balanced UVA-UVB sunscreens, absorbing over the entire UV spectrum are able to prevent or significantly reduce the associated biological damage.

Factors associated with premature skin aging (photoaging) before the age of 55: a population-based study.

BACKGROUND: Precise factors associated with premature skin aging, or photoaging, in the general population are unknown. OBJECTIVE: To examine the risk factors for photoaging in a Queensland community. METHODS: A cross-sectional study of 1,400 randomly selected residents aged 20-54 years, using casts of the back of the hand (surface microtopography) and dermatological assessment of photoaging. RESULTS: 83% of the participants had premature skin aging, worsening after the age of 30. Severe neck wrinkling was 3 times more likely in men and some 4 times more likely in fair-skinned people (odds ratio, OR=3.86, 95% confidence interval, CI=2.40-6.23). Red hair and mainly outdoor work or leisure raised the odds of microtopographic photoaging. Current smoking was strongly associated with facial comedones and telangiectasia, and among current smokers, the microtopography grade was significantly associated with moderate and heavy smoking measured by pack-years of exposure, with OR=3.18 (95% CI=1.38-7.35) in the heaviest (>20 pack-years) smoking category compared with 1-7 pack-years. CONCLUSIONS: Premature skin aging is common in the subtropics, more severe in men and the fair-skinned. It is associated with high sun exposure during leisure or work, and moderate to heavy smoking, and therefore is preventable.

Comparison of histological measures of skin photoaging.

BACKGROUND: Dermal elastosis is considered the histological 'gold standard' for evaluation of skin photoaging, but the relation of the level of dermal elastosis to other histological indicators of photoaging is not clear. OBJECTIVE: To investigate how various proposed histological measures of photoaging compare with the level of dermal elastosis. METHODS: Prospective, community-based study in Southeast Queensland, Australia, among 89 participants aged 40-82 years. Quantitative histology was used to evaluate 8 biomarkers of photoaged skin, and associations between grades of dermal elastosis and each of the other 7 biomarkers were analysed using ordinal logistic regression models with proportional odds assumption, using histological grades of elastosis as the outcome. RESULTS: Older age, male sex and high outdoor exposure levels were confirmed as predictors of high levels of dermal elastosis. After adjustment for age and sex, the only significant positive association with increasing elastosis grades was the proportion of p53-positive cells. Epidermal thickness, interdigitation index proportion of surface covered with melanin (% Fontana-Masson staining) and glycosaminoglycan content were not associated with elastosis in either crude or adjusted models. CONCLUSIONS: Among a range of suggested biomarkers of photoaged skin, only p53-positive cells appear to be strongly associated with the level of dermal elastosis.

Photodamage to human skin by suberythemal exposure to solar ultraviolet radiation can be attenuated by sunscreens: a review.

The effects of acute or repeated suberythemal solar ultraviolet radiation (UVR) exposure on human skin have been insufficiently investigated. Such exposure almost certainly has important long-term consequences that include skin ageing and skin cancer. This review summarizes the published data on the biological effects of suberythemal exposure using a wide range of clinical, cellular and molecular endpoints, some of which may be considered as biomarkers for skin cancer and photoageing. We also include some recent unpublished results from our laboratories. The effects of UVA (320-400 nm), UVB (290-320 nm) and total solar UVR (290-400 nm) are compared. We demonstrate that avoiding sunburn does not prevent many indicators of cutaneous biological damage and that use of low sun protection factor (SPF) sunscreen can inhibit much of the damages induced by suberythemal exposure to UVR. However, even when applied correctly, sunscreen use will result in suberythemal exposure. The degree and spectral quality of such exposure will depend on the SPF and absorption spectrum of the sunscreen, but nonetheless it may contribute to cumulative photodamage. This review may help to determine the level of photoprotection required in sunscreens and daily use products, as well as the ideal ratio of UVB/UVA protection, to improve long-term photoprotection outcomes.

A broad-spectrum sunscreen prevents cumulative damage from repeated exposure to sub-erythemal solar ultraviolet radiation representative of temperate latitudes.

BACKGROUND: We have previously shown the detrimental effects of 19 sub-erythemal exposures to daily ultraviolet radiation (DUVR, which mimics non-extreme exposure conditions), delivered over 4 weeks to volunteers. This source had UVA (320-400 nm) to UVB (290-320 nm) irradiance ratio of 25, instead of that close to 10 that is typically the case with solar-simulated radiation (SSR) that represents summer global sunlight with a clear sky and quasi-zenith solar irradiance. OBJECTIVE: Here, we report on an extension of this previous study, in which we evaluated the photoprotection afforded by a broad-spectrum daily-care product with a low-sun protection factor (SPF 8, UVA-PF 7 and 3* rated UVA protection). We assessed cellular and molecular markers of photodamage that are relevant to skin cancer and photoageing. RESULTS: This study shows that biological effects of repeated exposure to DUVR can be prevented by a broad-spectrum daily-care product and that the level of protection afforded varies with the studied endpoint. CONCLUSION: Efficient daily UVR protection, as provided by a broad-spectrum daily-care product, is necessary to prevent the 'silent' sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

Photoprotection in moisturizers and daily-care products.

During usual daily activities, an appropriate protection against solar UV exposure should prevent clinical, cellular and molecular changes potentially leading to photoaging. In skin areas regularly exposed to sun, UV-damage is superimposed to tissue degeneration resulting from chronological aging. It is, therefore, important to know if moisturizers and daily-care products containing UVA absorbers combined with UVB ones are able to prevent these skin damages. This review will summarize clinical studies evaluating this topic. These studies demonstrate that broad-spectrum protection in moisturizers or daily-care products can prevent the "silent" sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

Broad-spectrum sunscreens provide better protection from the suppression of the elicitation phase of delayed-type hypersensitivity response in humans.

It is well established that ultraviolet radiation has immunomodulatory effects that may be involved in skin cancer. Recent studies have shown that ultraviolet A radiation (320-400 nm) as well as ultraviolet B (290-320 nm) is immunosuppressive. This means sunscreens that mainly absorb ultraviolet B (protection against erythema) may be less effective in preventing ultraviolet radiation-induced immunosuppression than broad-spectrum products. We have studied the effects of ultraviolet A exposure on the human delayed-type hypersensitivity response and compared the efficacy of sunscreens having different levels of ultraviolet A protection under both solar-simulated radiation and outdoor real-life solar exposure conditions. Delayed-type hypersensitivity was assessed using recall antigens. In a first study, two groups of volunteers were exposed to ultraviolet A (either full spectrum ultraviolet A or ultraviolet A1) without prior application of sunscreen and they were shown to exhibit significantly reduced delayed-type hypersensitivity responses. In order to compare the efficacy of sunscreens in preventing photoimmunosuppression, three groups of subjects received 10 cumulative exposures to solar-simulated radiation; one group was exposed unprotected and the other two were exposed after being applied either a ultraviolet B or a broad-spectrum sunscreen, each with the same sun protection factor 9, but with different ultraviolet A protection factors 9 and 2. Then, an outdoor study was conducted in which delayed-type hypersensitivity was assessed before and after six daily exposures. Two different groups of subjects were treated with one of two sunscreens having the same sun protection factor 25 but different ultraviolet A-protection factors. In unprotected volunteers, responses to delayed-type hypersensitivity tests were significantly reduced irrespective of ultraviolet exposure conditions (full spectrum ultraviolet A, ultraviolet A1, solar-simulated radiation). The ultraviolet B sunscreen failed to protect from solar- simulated radiation-induced immunosuppression. In contrast, the broad-spectrum sunscreen having the same sun protection factor but providing high protection in the ultraviolet A range significantly reduced local ultraviolet-induced immunosuppression and prevented the distal effects. In the outdoor study, as compared with delayed-type hypersensitivity responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by broad-spectrum sunscreen sun protection factor 25 and ultraviolet A-protection factor 14. Conversely, a broad-spectrum sunscreen sun protection factor 25 ultraviolet A-protection factor 6 failed to protect against the sun-impaired response. The above studies clearly demonstrate the role of ultraviolet A in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire ultraviolet spectrum.

Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin.

All-trans retinoic acid (RA) has been shown to enhance subepidermal repair in photoaged hairless mice. The current study assesses the effects of RA on the glycosaminoglycan (GAG) content in irradiated and nonirradiated mouse skin. Mice were exposed to ultraviolet B (UVB) for 10 wk, after which they were treated either with 0.05% RA or with an ethanolpolyethylene glycol 400 vehicle three times a week for 10 or 20 wk. When assessed at the end of 10 wk of UVB irradiation, the GAG content had doubled, without a change in the hyaluronic acid (HA) to dermatan sulfate (DS) ratio. When irradiation was discontinued, the GAG content decreased progressively until the end of the experimental period. This decline was totally inhibited by RA treatment and could be ascribed to a marked increase in hyaluronic acid (78%), whereas no significant change in DS was observed. In nonirradiated skin, however, topical RA increased GAG levels mainly by a pronounced increase in the content (50%) and the synthesis (40%) of DS. In untreated mice, the HA/DS ratio decreased significantly with age in both irradiated and nonirradiated mice. Interestingly, RA maintained this ratio only in animals exposed to UVB. In addition, there was a marked stimulation in the heparin content, up to approximately 20-fold, after irradiation, whereas the amount of heparin in both irradiated and nonirradiated skin increased about 2- to 3-fold with RA treatment. In summary, the alterations induced in HA and DS contents in irradiated and nonirradiated skin indicate the specificity of the RA-induced effects for the various GAGs.

Eye-derived growth factor isolated from bovine retina and used for epidermal wound healing in vivo.

Eye-derived growth factor (EDGF) has been found in several ocular tissues and shown to be able to stimulate the in vitro proliferation of cells from various tissues and organisms. It had already been shown that EDGF differs biochemically and biologically from other growth factors such as epidermal growth factor (EGF) and fibroblast growth factor in that it is the only one that can stimulate the in vitro growth of human adult keratinocytes. Moreover EDGF stimulates reepithelialization and neovascularization. In this paper we report data concerning the effect on the rate of epidermal wound healing in guinea pigs of different extracts obtained from adult bovine retina. Our results show that EDGF can significantly increase the rate of reepithelialization when epidermis is detached from dermis and removed after induction of a blister. The doses used were comparable to the ones used to obtain maximal increase of cell proliferation in vitro. However no attempt was made to further investigate the mechanism accounting for the observed wound healing. At 24 h, control wounds maintained under occlusive dressing had only about 50% of their surface covered with cells as opposed to EDGF-treated wounds which were covered up to about 80% (p = 0.05). On the other hand, EGF does not increase the rate of wound healing in this model even at 1000-fold higher doses than those used in in vitro bioassays. Although EDGF is still not purified to homogeneity and another 10- to 100-fold purification might be necessary to achieve homogeneity, our results suggest that EDGF may find therapeutic applications as a potent in vivo epidermal wound healing agent.

Improved protection against solar-simulated radiation-induced immunosuppression by a sunscreen with enhanced ultraviolet A protection.

Ultraviolet radiation-induced immunosuppression is thought to play a part in skin cancer. Several studies have indicated that sunscreens that are designed to protect against erythema failed to give comparable protection against ultraviolet radiation-induced immunosuppression. One possible reason for this discrepancy is inadequate ultraviolet A protection. This study evaluated the level of immunoprotection in mice afforded by two broad-spectrum sunscreens with the same sun protection factor, but with different ultraviolet A protection factors. Both sunscreens contained the same ultraviolet B and ultraviolet A filters, in the same vehicle, but at different concentrations. Solar simulated radiation dose-response curves for erythema, edema, and systemic suppression of contact hypersensitivity were generated and used to derive protection factors for each end-point. The results of three different techniques for determining immune protection factor were compared. A comparison of the two sunscreens showed that the protection factor for erythema in mice was similar to that determined in humans (sun protection factor) but the protection factor for edema in mice was lower. Both sunscreens protected against suppression of contact hypersensitivity but the product with the higher ultraviolet A-protection factor showed significantly greater protection. The three techniques for determining immunoprotection gave very similar results for a given sunscreen, but immune protection factor was always lower than sun protection factor. These data suggest that sun protection factor may not predict the ability of sunscreens to protect the immune system and that a measure of ultraviolet A protection may also be necessary.

Inhibition of solar simulator-induced p53 mutations and protection against skin cancer development in mice by sunscreens.

We demonstrated previously that p53 mutations can be detected in ultraviolet B-irradiated mouse skin months before the gross appearance of skin tumors and that applying sun protection factor 15 sunscreens to mouse skin before each Kodacel-filtered FS40 sunlamp irradiation resulted in the reduction of such mutations. To determine whether there is an association between reduction of ultraviolet-induced p53 mutations by sunscreens and protection against skin cancer using an environmentally relevant light source, we applied sunscreens (sun protection factors 15-22) on to the shaved dorsal skin of C3H mice 30 min before each exposure to 4.54 kJ ultraviolet B (290-400 nm) radiation per m2 from a solar simulator. Control mice were treated 5 d per wk with ultraviolet only or vehicle plus ultraviolet. p53 mutation analysis indicated that mice exposed to ultraviolet only or vehicle plus ultraviolet for 16 wk (cumulative exposure to 359 kJ ultraviolet B per m2) developed p53 mutations at a frequency of 56%-69%, respectively, but less than 5% of mice treated with sunscreens plus ultraviolet showed evidence of p53 mutations. More importantly, 100% of mice that received a cumulative dose of 1000 kJ ultraviolet B per m2 only, or vehicle plus ultraviolet B developed skin tumors, whereas, the probability of tumor development in all the mice treated with the sunscreens plus 1000 kJ ultraviolet B per m2 was 2% and mice treated with sunscreens plus 1500 kJ ultraviolet B per m2 was 15%. These results demonstrate that the sunscreens used in this study not only protect mice against ultraviolet-induced p53 mutations, but also against skin cancers induced with solar-simulated ultraviolet. Because of this association, we conclude that inhibition of p53 mutations is a useful early biologic endpoint of photoprotection against an important initiating event in ultraviolet carcinogenesis.

Age-dependent variations of the biosyntheses of fibronectin and fibrous collagens in mouse skin.

Skin explant cultures from hairless mice of increasing age were incubated with radioactive precursors in order to determine the age-dependent variations of the biosyntheses of fibronectin and fibrous collagens (types I and III). Total collagen synthesis expressed as a percentage of total protein synthesis did not vary with age but, if expressed as micrograms hydroxyproline per mg wet weight of skin, decreased by about 30% between 2 and 22 months of age. Hydroxylation of collagen, expressed as the ratio of 3H-hypro over 3H (pro + hypro) incorporated in freshly synthesized collagen, decreased with age by about 40% between 2 and 22 months of age. The proportion of type III collagen expressed as % of type I + type III collagens increased progressively with age by about 25% at 12 months to 60% at 22 months of age. Fibronectin biosynthesis, determined by immunoprecipitation of 35S-methionine labeled peptides in SDS-extracts of skin increased progressively with age from about 2% of total incorporated radioactivity in fibronectin at 2 months to 4% at 22 months. Plasma fibronectin, of hepatic origin, was shown already to increase with age in humans. It appears thus that the expression of genes coding for extracellular matrix macromolecules is under age-dependent regulation. This regulation appears to be different for the investigated macromolecules.

Mexoryl SX protects against solar-simulated UVR-induced photocarcinogenesis in mice.

The aim of this study was to determine, for regulatory purposes, the potential of Mexoryl SX, a broad UVA absorber that also absorbs to some extent in the UVB, to modify the UV radiation (UVR)-induced murine skin tumor development and growth. Skh-hr1 mice were exposed to solar-simulated UVR 5 days per week for 40 weeks. Two control groups were irradiated without topical application, three groups received a sunscreen preparation containing either the UVA absorber, Mexoryl SX at 5 or 10% concentration, or a filter that absorbs principally in the UVB, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) at 5% concentration, introduced as a comparator test article. Sunscreen application was performed before UVR exposure 3 days per week and after UVR exposure on the other 2 days (consistent with the design of a standard photocarcinogenesis safety test). Two different weekly UVR doses were administrated: the lower dose was given to one group of unprotected animals, whereas the higher dose was administrated to the other unprotected group and to the three sunscreen-treated groups. The two UVR control groups demonstrated a UVR-dependent response for cumulative tumor prevalence, tumor yield and median latent period. Neither concentration of Mexoryl SX increased the probability of tumor development; consistent with the principles for safety testing, this provides evidence in that it is safe for use in sunlight. Although this study was explicitly designed as a safety test, the results also provide some clues about the efficacy of Mexoryl SX in decreasing the probability of tumor development. Topical administration of Mexoryl SX, at both concentrations, resulted in a 6 week delay in the median latent period compared to high UVR controls, whereas 5% 2-EHMC delayed the median latent periods only by 2 weeks. Tumor prevalence and yield show the same efficacy differences between the two sunscreen ingredients. Tumor protection factors were calculated from these results and found to be equal to 2.4 for the two preparations containing Mexoryl SX and to 1.3 for the 5% 2-EHMC preparation. These findings illustrate the efficacy of Mexoryl SX in preventing UVR-induced carcinogenesis.

Miniature pig as an animal model to study photoaging.

Seven miniature pigs were irradiated thrice weekly over a 14 months period with suberythematogenic doses of UVB and UVA. Another seven were not exposed, to record innate aging changes. Chronic irradiation induced the following changes: 1. Increased scaling, with thickening of the stratum corneum and decreased reactivity to acetic acid. 2. Increased minimum erythema dose, corresponding to decreased transmission of UV-radiation through isolated epidermis. 3. Increased elastic fibers, accompanied by strong deposition of glycosaminoglycans in the upper dermis. 4. Increased laxity with greater extensibility to a deforming torque. 5. Increased density of vessels. 6. More disorderly arrangement of collagen bundles with minor alterations in collagen biochemistry. These changes mimic those in photoaged human skin but are milder in degree, attributable to the low total dosage of ultraviolet radiation.

UVAI-induced edema and pyrimidine dimers in murine skin.

The induction of edema and pyrimidine dimers in epidermal DNA was determined in the skin of SKH:HR1 mice exposed to graded doses of ultraviolet radiation AI (UVAI; 340-400 nm). Exposure to UVAI induced 1.6 +/- 0.08 x 10(-6) (mean +/- standard error of mean) pyrimidine dimers per 10(8) Da of DNA per J/m2. Edema in irradiated animals was determined as an increase in skinfold thickness. A dose of 1.8 x 10(6) J/m2 of UVAI that resulted in a 50% increase in skinfold thickness (SFT50%) would have induced 1.0 x 10(5) dimers per basal cell genome. A similar increase in SFT induced by full spectrum solar ultraviolet radiation (290-400 nm) would accompany the induction of 11.0 x 10(5) pyrimidine dimers per basal cell genome. These results support a hypothesis that UVAI-induced pathological changes of the skin are mediated through the formation of nondimer photoproducts.

Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA.

Pyrimidine dimers were measured in epidermal DNA of SKH:HR1 mice following exposure to solar-simulated UV radiation (SSUV, 290-400 nm) or to UVA (320-400 nm). Mice were exposed to SSUV or UVA after topical application (2 mg/cm2) of vehicle, a UVB absorber (5% 2-ethylhexyl p-methoxycinnamate [2-EHMC]), or a broad-spectrum UVA absorber (5% Mexoryl SX). The rates of induction of pyrimidine dimers in untreated animals were 5.4 +/- 0.57 x 10(-4) (mean +/- SEM) and 7.6 +/- 0.95 x 10(-6) dimers per 10(8) Da of epidermal DNA per J/m2 of SSUV and UVA, respectively. Topical application of Mexoryl SX reduced the rate of induction of pyrimidine dimers in SSUV-exposed animals to 4.7 +/- 0.44 x 10(-5) dimers per 10(8) Da per J/m2 for a dimer induction protection factor (PF) of 11.5 (5.4 x 10(-4)/4.7 x 10(-5). The rate of dimer induction in Mexoryl SX-treated, UVA-exposed mice was 0.95 +/- 0.2 x 10(-6) dimers per 10(8) Da per J/m2 (PF = 8.0). The 2-EHMC at a concentration of 5% (wt/wt) was significantly less effective than Mexoryl SX in preventing the induction of pyrimidine dimers in animals exposed to either SSUV or UVA. The rates of dimer induction in 2-EHMC-treated mice were 8.2 +/- 1.1 x 10(-5) and 3.8 +/- 0.33 x 10(-6) dimers per Da per J/m2 of SSUV (PF = 6.6) and UVA (PF = 2.0), respectively. Upon normalizing to the efficacy for edema induction, UVA induced approximately one-fourth the number of pyrimidine dimers per equivalent edematous response when compared to SSUV.

Alterations of proteoglycans in ultraviolet-irradiated skin.

The effect of UVB exposure on the distribution and synthesis of dermal proteoglycans was measured in the skin of hairless mice. Two groups of mice were included: one was irradiated for 10 weeks; the other was kept as control. After intraperitoneal injection of sodium 35-S-sulfate, punch biopsies were taken for histology and proteoglycans were extracted from the remaining skin with 4 M guanidinium chloride, containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (0.5%, weight per volume). Following proteolytic digestion, the glycosaminoglycan constituents were isolated and analyzed by quantitative cellulose acetate electrophoresis and enzymatic digestibility. Under the influence of UVB radiation, newly synthesized proteoglycans measured by 35SO4 uptake increased as much as 60%. In addition, the irradiated skin had a higher average content of proteoglycan than had control skin (4981 micrograms vs 4134 micrograms/g dry weight). This could be ascribed to an increase in heparin (1400 vs 533 micrograms/g dry weight) and heparan sulfate (472 vs 367 micrograms/g dry weight), whereas no change in the concentration of hyaluronic acid (1243 vs 1372 micrograms/g dry weight) and dermatan sulfate (1866 vs 1863 micrograms/g dry weight) was observed. The irradiated animals also exhibited a marked increase in the synthesis of heparan sulfate and heparin (62% and 71%, respectively). These results demonstrate that chronic doses of UVB altered proteoglycan metabolism through both quantitative and qualitative changes.

In vivo evaluation of photoprotection against chronic ultraviolet-A irradiation by a new sunscreen Mexoryl SX.

In a previous study on the hairless mouse it was shown that sub-erythemal doses of pure UV-A enhanced the numerous changes normally observed during chronological aging. A new sunscreen (a bis-benzylidene campho sulfonic acid derivative) has been synthesized in our research laboratory (lambda max: 345 nm, epsilon: 47,000). Its photoprotective properties against UV-A induced damages were assessed in our mouse model. Three month old albino hairless mice were exposed for 1 y to suberythemal doses (35 J/cm2) of UV-A obtained from a xenon source filtered through a WG 345 filter. One group of animals was exposed untreated, the other received a formulation containing 5% of the sunscreen prior to irradiation. At the end of the study the cutaneous properties of protected mice were compared to those of unprotected animals and to 3 and 15 month old unirradiated controls. We found that the visible changes induced by UV-A irradiation were mainly sagging and wrinkling. Histological and electron microscopic alterations consisted of hyperkeratosis, increased density of elastic fibers with alteration of fiber orientation and increased glycosaminoglycan deposits. Biochemical changes consisted of decreases in total collagen and collagen hydroxylation and increases in both collagen III/I + III ratio and fibronectin biosynthesis. All these changes were reduced or abolished by the sunscreen.

Direct comparison of DNA damage, isomerization of urocanic acid and edema in the mouse produced by three commonly used artificial UV light sources.

Exposure to sunlight can result in a number of harmful effects, including sunburn, erythema, premature aging of the skin, immune suppression and skin cancer. Studies designed to understand the underlying mechanisms often depend upon the use of artificial sources of UV radiation. Unfortunately, conclusions from different laboratories using different lamps often conflict, and it is entirely possible that the different spectra of sunlights used in each may be a source of conflict. To minimize confounding variables, we employed two of the more commonly used UV light sources, fluorescent sunlamps, such as the FS-40 and Kodacel-filtered FS-40 sunlamps, and a xenon arc solar simulator and compared, in one series of standardized experiments, the effects of each light source on DNA damage, urocanic acid isomerization and edema formation. The dose-response curves, calculated by linear regression or curve fitting were compared. The data indicate that DNA damage and urocanic acid isomerization were more sensitive to shorter wavelengths of UV than longer wavelengths, and the biological endpoint of edema most closely correlated with the induction of DNA damage. The results emphasize the dominance of shorter wavelengths within the UV spectrum in damaging biological tissues, even when the solar simulator, which contains significant amounts of UVA, was used and demonstrate that each light source has a characteristic pattern of induction of biochemical and biological endpoints.

p53 Mutations in hairless SKH-hr1 mouse skin tumors induced by a solar simulator.

In this study, we investigated whether the spectrum of p53 mutations in skin tumors induced in hairless SKH-hr1 mice by a solar simulator (290-400 nm) are similar to those found in skin tumors induced in C3H mice by UV radiation from unfiltered (250-400 nm) and Kodacel-filtered (290-400 nm) FS40 sunlamps. Analysis of tumor DNA for p53 mutations revealed that 14 of 16 (87.5%) SkH-hr1 skin tumors induced by the solar simulator contained mutations. Single C-->T transitions at dipyrimidine sequences located on the nontranscribed DNA strand were the most predominant type of p53 mutation. Remarkably, 52% of all p53 mutations in solar simulator-induced SKH-hr1 skin tumors occurred at codon 270, which is also a hotspot in C3H skin tumors induced by unfiltered and Kodacel-filtered FS40 sunlamps. However, T-->G transversions, which are hallmarks of UVA-induced mutations, were not detected in any of the solar simulator-induced skin tumors analyzed. These results demonstrate that the p53 mutation spectra seen in solar simulator-induced SKH-hr1 skin tumors are similar to those present in -unfiltered and Kodacel-filtered FS40 sunlamp-induced C3H skin tumors. In addition, our data indicate that the UVA present in solar simulator radiation does not play a role in the induction of p53 mutations that contribute to skin cancer development.