Anny Fourtanier

Broad-spectrum sunscreens provide better protection from solar ultraviolet–simulated radiation and natural sunlight–induced immunosuppression in human beings

BACKGROUND It is well established that ultraviolet (UV) radiation induces immunomodulatory effects that may be involved in skin cancer. Recent studies have shown that UVA (320-400 nm) and UVB (290-320 nm) radiation are immunosuppressive. As a result, sunscreens, which mainly absorb UVB, may be less effective in preventing UV radiation-induced immunosuppression than broad-spectrum products. OBJECTIVE We sought to study the effects of UVA exposure on human delayed-type hypersensitivity (DTH) response and compare the efficacy of sunscreens having different levels of sun-protection factor (SPF) and UVA protection against both solar-simulated radiation and outdoor real-life sunlight exposure conditions. METHODS DTH was assessed using a kit which includes 7 recall antigens that most of the participants encountered during childhood immunization. Evaluation of DTH test response was made 48 hours after test application before and after UV exposure with or without sunscreens. RESULTS In unprotected participants, the response to DTH tests was significantly reduced irrespective of UV types of exposure (full-spectrum UVA, long UVA, solar-simulated radiation). A UVB sunscreen failed to protect from solar-simulated radiation-induced immunosuppression. In contrast, a broad-spectrum sunscreen with the same SPF but providing a high protection in the UVA range significantly reduced local UV-induced immunosuppression and prevented the distant effects. In the outdoor study, as compared with DTH responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by a broad-spectrum sunscreen having a high protection level in the UVA (SPF 25, UVA protection factor 14). Conversely a broad-spectrum sunscreen with lower protection against UVA (SPF 25, UVA protection factor 6) failed to prevent UV-impaired response. LIMITATIONS These results have been obtained after repeated exposure. Additional experiments obtained under acute exposure are in progress. CONCLUSION These findings clearly demonstrated the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum.

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.

MEXORYL SX : A BROAD ABSORPTION UVA FILTER PROTECTS HUMAN SKIN FROM THE EFFECTS OF REPEATED SUBERYTHEMAL DOSES OF UVA

There is now considerable evidence that chronic UVA exposure induces damage in animal and human skin; however, little is known about UVA protection of human skin. The aim of this study is to evaluate the efficacy of Mexoryl SX, a broad UVA absorber (lamada max = 345 nm) against UVA-induced changes in human skin. The regimen of UVA exposure (13 weeks with increasing suberythemal doses) induces intense pigmentation with no erythema. Skin hydration and elasticity decrease, whereas total skin thickness, assessed by echography, remains unchanged. Irradiated epidermis reveals a significant thickening of the stratum corneum, an absence of hyperplasia and an increase in the expression of the protective iron-storage protein ferritin. No significant alterations are seen using antisera against type IV collagen or laminin, suggesting that the dermal-epidermal junction (DEJ) is mainly preserved. In dermis, enhanced expression of tenascin is seen just below the DEJ but type I procollagen, which is localized at the same site, is unaltered. Although we are unable to visualize any changes in elastic network organization using Luna staining or specific antiserum directed against human elastin, we notice an increased deposition of lysozyme or alpha-1 antitrypsin on elastin fibres. Mexoryl SX (5%) efficiently prevents these alterations. Thus, these results suggest that UVA photoprotection can prevent early putative alterations leading to photoageing.

Alterations in human epidermal Langerhans cells by ultraviolet radiation: quantitative and morphological study

Summary Background Ultraviolet (UV) exposure of human skin induces local and systemic immune suppression. This phenomenon has been well documented when UVB radiation (290–320 nm) is used. The mechanism is thought to involve Langerhans cells (LCs), the epidermal dendritic cells that play a crucial role in antigen presentation. A variety of studies have clearly demonstrated that UVB radiation decreases LC density and alters their morphology and immunological function, but little is known about the effects of the entire UV spectrum (ultraviolet solar simulated radiation, UV‐SSR or UVB + UVA) or UVA (320–400 nm) radiation alone.

A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging

Background: There is overwhelming evidence that exposure of human skin to ultraviolet radiations (UVR) leads to the development of cutaneous photoaging and eventually to neoplasia. This study was designed to evaluate in humans the protection afforded by a daily use cream containing a photostable combination of UVB and UVA absorbers (Uvinul® N539, Parsol® 1789 and Mexoryl® SX) providing a continuous absorption through the entire UV spectrum, against damages induced by repeated daily exposure to solar simulated radiation (SSR).

Age dependent increase of elastase type protease activity in mouse skin. Effect of UV-irradiation.

The effect of chronological aging and photoaging (UV-radiation) on elastase-type enzyme activity of hairless mouse skin was studied. Aging resulted in the increase of elastase type endopeptidase activity extractable from mouse skins. Both chronic UVA and UVB radiation resulted in a significant increase of elastase type activity. PBS extracted only small part of the elastase activity, UV-A produced an increase of about 90-120% according to the type of irradiation (xenon or UV-A SUN) and UV-B produced a 72% increase. Extraction by Triton X-100 suggested that most of the activity is bound to cells and fibrous structures. EDTA inhibited 80-90% of the elastase activity in chronologically aged skin extracts and also the activity induced by UVA radiation suggesting that metallo-elastase(s) are involved. About 30% of the UVB induced activity could only be inhibited by EDTA and about 50% by PMSF suggesting that irradiation by UVB increased more serine endopeptidase activity but also MMP-activity. Chronic UVA radiation produced an increase of skin elastase activity equivalent to that observed after 24 months of aging in non-irradiated animals (approximately 100 weeks) corresponding to approximately 90% of total life span of these mice. The total increase produced by UVB was less, but the strong increase of a serine elastase, presumably from PMN-s, appear to produce a much more pronounced biological activity as shown by the presence of fibronectin degradation products in skin extracts. Such degradation products were shown to exert harmful effects on tissues. These results may well have biological significance and distinguish chronological aging and photoaging.

Sunscreens containing the broad-spectrum UVA absorber, Mexoryl® SX, prevent the cutaneous detrimental effects of UV exposure : a review of clinical study results

Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones.

Accumulated p53 protein and UVA protection level of sunscreens

Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)‐induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA‐PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA‐PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53‐positive cells was found in areas protected with the sunscreen having the higher UVA‐PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320–400 nm) or UVA1 (340–400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53‐positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA‐induced cell damage.

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 Kodacelfiltered (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.

MINIATURE PIG AS AN ANIMAL MODEL TO STUDY PHOTOAGING

Abstract— Seven miniature pigs were irradiated thrice weekly over a 14 months period with suberythem‐atogenic doses of UVB and UVA. Another seven were not exposed, to record innate aging changes.