[Solar protection products: efficacy and risks]. / Produits de protection solaire : efficacité et risques.

Solar protection products (SPP) containing chemical filters and/or mineral filters are extensively used today in photoprotection; however, concerns continue to be voiced about their efficacy and about their possible dangers. A rapid review of photoprotection strategies shows that SPP owe their photoprotective effect to the absence of other photoprotection methods having clearly established efficacy in healthy subjects; in addition, they exhibit real protective efficacy against the majority of harmful effects of solar radiation, provided they have been devised in keeping with the specifications clearly set out in the recommendations of the French Medicines Agency (Afssaps). Such efficacy is dependent on their correct usage, recently reiterated by Afssaps in its recommendations to end-users concerning the good use of solar products: application of adequate quantities of such products, selection of the appropriate photoprotection class based on phototype and conditions of exposure, and regular renewal of applications in the event of prolonged exposure and after bathing or profuse sweating. Solar filters have long been known to cause contact allergic dermatitis, irritative dermatitis and photosensitisation, and a particular risk has appeared with the use of octocrylene. However, debate has centred primarily on the risk of endocrine disturbance potentially induced by chemical filters, certain of which exhibit established transcutaneous penetration. The risk of mimicry of an effect of oestradiol has been raised on the basis of a series of studies, almost all of which were carried out by the same team, and which mainly concerned 4-methylbenzylidene-camphor (4-MBC) following oral absorption in the rat. The risk of this type of effect with SPPs under normal conditions of use seems fairly remote according to the current state of knowledge; in any event, within the context of the "National Fertility Action Plan", Afssaps has been formally requested to analyse the risk associated with cosmetic substances that are "reprotoxic" and/or affect endocrine function, as a result of which various filters are currently being reassessed for such risk. The greater alleged safety of mineral filters, based on the absence of introduction of risk of photosensitisation (as a result of which they are preferred for use in young children), no longer seems so clear since the introduction of titanium dioxide (TiO2) and zinc oxide (ZnO) in the form of nanoparticles. Afssaps drew up a risk assessment report concerning cutaneous penetration, genotoxicity and oncogenesis for TiO(2) and ZnO in nanoparticle form; further studies are needed before any general conclusions may be drawn. The European Scientific Committee on Consumer Safety (SCCS) is also carrying out an evaluation of the use of TiO(2) and of ZnO as UV filters. Finally, current data do not suggest that SPPs exert any harmful effects by inhibiting the beneficial effects of the sun, in particular, vitamin D synthesis.

[Narrow-band UVB therapy in psoriasis vulgaris: good practice guideline and recommendations of the French Society of Photodermatology]. / La photothérapie UVB à spectre étroit dans le psoriasis vulgaire : utilisation pratique et préconisations de la Société Française de Photodermatologie.

BACKGROUND: Phototherapy, PUVA therapy and narrow-band UVB are recognised forms of first-line therapy for extensive and severe plaque psoriasis. Based on a systematic review of the medical literature, we propose a good practice guideline for the use of narrow-band UVB phototherapy in this indication. METHODS: We carried out a review of the literature published over the 20 years (1998 to 2009) in the online PubMed database. Our conclusions are based on the results of control studies or where these are absent, on a synthesis of the recommendations common practice approved by the experts of the French Society of Photodermatology. The levels of scientific proof given are based on the criteria defined by Sackett. RESULTS RECOMMENDATIONS: (1) Practical aspects. Irradiation cabins equipped with Philips TL01 tubes, either for monotherapy (42 tubes) or for combined therapy (21 UVB tubes and 21 UVA tubes), were to be certified (CE marking, ISO-DIN certification) and equipped with an accurate dosimetry system. Several valid and usable protocols exist. The indication was based on the severity and extent of the episode of psoriasis, the psychological consequences of the dermatosis, comparison of the benefit/risk ratios of the various available treatments, the ability of the patient to attend sessions (a vital factor in therapeutic compliance), the cumulative doses of UV from previous courses of treatment, and absence of contraindications, including the use of photosensitising medication. Informed consent was to be obtained from patients, who were given a validated information sheet (available at www.sfdermato.org). The study results and the value of maintenance therapy were not confirmed. (2) Adverse effects. The immediate adverse effects were generally of little consequence, with later effects alone posing problems. Because of the risk of induction of cataract, ocular protection must be used during sessions. In the absence of symptoms or known ocular disorder, prior ophthalmologic control is not considered necessary. The risk of skin cancer remains poorly defined, and this risk has not been clearly shown to be lower than with broad-spectrum UVB therapy or PUVA. The studies give no indication of the number of sessions after which therapy must be completely discontinued. In the absence of clear evaluation of oncogenic risk, it seems reasonable to set the maximum number of sessions of UVB TL01 phototherapy at 250 as with PUVA, and to include in this limit the total of all PUVA and TL01 phototherapy sessions for patients receiving both types of phototherapy (level of proof: B). In the absence of lesions requiring treatment in these areas, the face and male genital organs should be protected during treatment sessions. There is no currently available data concerning carcinogenic risk induced by TL01 in patients also on cyclosporine, methotrexate or biotherapies. In order to reduce risk and maintain patients' capacity to undergo further phototherapy sessions, we suggest (level of proof: A) the following measures: strict patient selection, use of combined synergistic therapies, annual examination of the skin and appendages of subjects receiving more than 150 phototherapy sessions, and the creation of nationally accessible patient phototherapy files. (3) Combined treatments. The purpose of such treatment is twofold: to reduce the risk of adverse effects while increasing the efficacy of TL01 phototherapy. Lesions should be sloughed before the start of phototherapy. Synergistic effects have been demonstrated for dermal corticosteroids and tazarotene, but such effects are less noticeable with topical vitamin D3 derivatives. If there are no contraindications to its prescription, we feel that acitretine has demonstrated efficacy in enhancing the effect of TL01 phototherapy. (4) Efficacy. Narrow-spectrum UVB phototherapy is considered highly effective in extensive psoriasis. At a rate of three sessions per week, it results in complete (or almost complete) eradication of lesions in 60 to 90 % of patients within 20 to 40 sessions (level of proof: A). However, the efficacy of this therapy varies according to plaque size and noticeably better results are obtained in guttate and nummular psoriasis than in psoriasis involving large plaques. CONCLUSION: Narrow-spectrum UVB phototherapy offers a good alternative to PUVA therapy since concomitant psoralen is not required, but there are few immediate adverse effects, there is less risk of drug-induced photosensitisation, and there is no need for skin or ocular photoprotection after sessions. We recommend this approach as the first-line phototherapy (level of proof: A) in children and adolescents, and in adults with extensive moderate psoriasis involving small superficial plaques. It may also be used in pregnant or breastfeeding women and in patients with renal or hepatic insufficiency. In addition, it is preferable for HIV-positive subjects (level of proof: C). However, PUVA therapy is preferable as first-line treatment in extensive severe psoriasis involving large thick plaques (level of proof: A) and in adults of phototypes IV to VI (level of proof: B); it should also be contemplated for psoriasis refractory to UVB TL01 (level of proof: B).

[Circumscribed telangiectasic lesions of the upper limb: unilateral nevoid telangiectasia syndrome?]. / Lésions télangiectasiques circonscrites au membre supérieur: penser au syndrome des télangiectasies naevoïdes unilatérales.

Patients presenting skin disorders with a probably vascular origin are often addressed to the vascular medicine unit. In general, the diagnosis of telangiectasia is straightforward but in certain rare clinical forms may be misleading. We report the case of a female patient presenting unilateral circumscribed telangiectasia on the left arm. History taking revealed that these lesions were congenital and had become accentuated during a recent pregnancy. The unilateral localization was highly suggestive, following Blaschko's lines. We retained the diagnosis of congenital unilateral nevoid telangiectasia syndrome exaggerated by pregnancy and the consequent hyperestrogenism. While it may be rather easy to rule out medical emergencies such as purpura, identifying the etiology of telangiectasia may be quite difficult, implying a careful, precise and complete history taking. Unilateral nevoid telangiectasia is a rare entity to be recognized. The underlying pathogenic mechanism remains to be elucidated.

[Febrile cellulitis surrounding a scar revealing a large immunoblastic B-cell lymphoma]. / Dermohypodermite fébrile péricicatricielle révélatrice d'un lymphome B immunoblastique à grandes cellules.

BACKGROUND: Secondary skin sites of lymphoma appear in the advanced stages of the disease. We report the first case of a pericicatricial skin infiltration, mimicking febrile dermohypodermitis, revealing diffuse immunoblastic large B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Four months after decompressive cervical laminectomy, a 56-year-old man presented an inflammatory pericicatricial patch evoking cellulitis in a setting of hyperthermia and lymphadenopathy. Blood cultures and bacteriological analysis of skin biopsy samples were negative. The images showed infiltration of the soft subcutaneous areas and polyadenopathy. Two weeks later, several subcutaneous nodules appeared on the trunk. Histological analysis and immunolabelling pointed to immunoblastic large B-cell non-Hodgkin's lymphoma. A clone of B lymphocytes CD45+, CD20+, CD79a+, Bcl2+, CD5+, MUM1+, CD3-, CD10-, CD23- and Bcl6- was seen. The remainder of the extension examination was negative. CHOP-rituximab polychemotherapy resulted in complete regression of all lesions, notably the inflammatory cervical plaque. DISCUSSION: Secondary skin manifestations of lymphoma are generally non-specific (pruritus, ichthyosis, purpura, etc.) rather than specific in terms of lymphoid infiltration. As in our patient, certain cutaneous sites of lymphoma may have a misleading clinical presentation, histological analysis alone was able to provide a conclusive diagnosis. In our patient, the highly specific infiltration seen around the entire scar could either suggest a Koebner phenomenon or point to a role of the cutaneous aggression within the development of an inflammatory process contributing to pericicatricial infiltration by lymphoid cells. Locoregional invasion from the osseous part of the cervical spine and not macroscopically diagnosed during neurosurgery could also be responsible.

[Dermatologic follow-up and evaluation of skin tumours in renal transplant patients]. / Evaluation du suivi dermatologique et des tumeurs cutanées chez les greffés rénaux.

BACKGROUND: Renal transplant patients are at increased risk for warts, actinic keratoses and carcinomas. A descriptive study was conducted to investigate the number and frequency of dermatologic examinations in renal transplant patients with a functional graft. The incidence and clinical factors for skin tumours were also assessed. PATIENTS AND METHODS: We sent an initial questionnaire to 686 renal transplant patients asking whether they had consulted a dermatologist since the time of transplantation. A second questionnaire was then sent to private dermatologists in order to evaluate dermatologic follow-up and the frequency and anatomic distribution of warts and cancerous skin lesions. At the same time, the patients' medical records at the hospital were studied. RESULTS: About two thirds of the 436 patients included in the study have seen a dermatologist at least once since the time of transplantation. Only 31.2% are being followed up regularly by a dermatologist. The incidence of warts and actinic keratoses is 48.8% and 20.6% respectively, and increases with the duration of immunosuppressive therapy. The incidence of carcinomas is 20.2%, with basal cell carcinomas being seen more frequently than other carcinomas. Risk factors identified for carcinomas are older age at transplantation, duration of immunosuppressive therapy, fair skin, presence of warts and actinic keratoses. All these skin lesions arise predominantly on highly sun-exposed surfaces. Nevertheless, squamous cell carcinomas are more often confined to sun-exposed skin than Bowen's diseases and basal cell carcinomas. DISCUSSION: Dermatologic follow-up of transplant recipients has rarely been investigated and our study shows that monitoring of skin cancer is probably inadequate. It also confirms the high incidence of carcinomas among renal-transplant recipients in a temperate climate, although basal cell carcinomas are more frequent than squamous cell carcinomas.

[Syringotropic and pilotropic cutaneous T-cell lymphoma without follicular mucinosis]. / Mycosis fongoïde syringotrope et pilotrope sans mucinose folliculaire.

BACKGROUND: Mycosis fongoides rarely exhibits predilection for infiltration of hair follicles and eccrine glands. We report the case of a patient with cutaneous T-cell lymphoma with syringotropism and pilotropism without follicular mucinosis. CASE REPORT: A 51-year-old man presented with erythematous infiltrated patches with alopecia and anhydrosis, cystic lesions, comedon-like lesions, follicular keratosis and an ulcer over the lower left leg. Clinical examination revealed no palpable adenopathy or hepatosplenomegaly. The patient complained about hypohydrosis. Histological examination of skin biopsies evidenced pilotropic cutaneous T-cell lymphoma without follicular mucinosis. Immunohistological examination and T-cell receptor B-chain gene rearrangement analysis showed a clonal population of T-cells. Moreover sweat glands and sweat ducts were infiltrated by atypical lymphocytes with syringolymphoid hyperplasia. DISCUSSION: Syringolymphoid hyperplasia and folliculotropism without follicular mucinosis are rarely seen in mycosis fongoides. Deep biopsies of adnexal structures are required for this critical diagnosis and clonal rearrangement of TCR genes is a reliable means of assessing clonality. Syringolymphoid hyperplasia and pilotropism without mucinosis are variants of cutaneous T-cell lymphomas.

[Polymorphic light eruption: prophylaxis using a topical combination of antioxidants and UVA protection formulations]. / Lucite estivale bénigne: prévention par un topique associant des filtres anti-UVA et des antioxydants.

BACKGROUND: In a recent randomized, double-blind, placebo-controlled clinical study, the efficacy of a combination consisting of 0.25% alpha-glucosyl-rutin, 1% vitamin E and a broad-spectrum, highly UVA-protective sunscreen (sun protector factor 15 - persistent pigmentation darkening 6) regarding prevention of polymorphous light eruption was well demonstrated. We evaluated this combination under real solar exposure conditions. PATIENTS AND METHODS: Patients with three previous typical polymorphous light eruptions (including one in the last year) were included in an open prospective multicenter study. The preparation was applied every two hours after the first summer exposure. No topical or systemic treatments presumed to be effective against polymorphous light eruption were given concomitantly. Evaluation was performed after the summer by a dermatologist. RESULTS: Two of the 54 patients dropped out of the study, one for an adverse effect (contact dermatitis). At the end of the study following application of the test preparation, no eruption was seen for 35 patients (67%), with minor eruption for 10 patients (19%) and an marked eruption for 7 patients (13%). Pruritus (present in all patients the year before) was not seen in 36 patients (69%), was considered bearable for 36 patients and unbearable for only 3 patients compared to 27 before inclusion. For the dermatologists, efficacy was excellent for 35 patients and good for 7 patients, giving global efficacy of around 80%, with inadequate results in 10% of cases (5 patients). Concerning protection against erythema, the test product reduced sunburn by 60% compared with the previous year. DISCUSSION: Because of the high clinical efficacy of the product noted after UVA challenge tests and verified by this clinical study under actual conditions of exposure, it may be proposed as a new prophylactic treatment for polymorphous light eruption.

[Acrodermatitis enteropathica-like syndrome secondary to branched-chain amino acid deficiency during treatment of maple syrup urine disease]. / Pseudo-acrodermatite entéropathique secondaire à un déficit en acides aminés ramifiés au cours du traitement d'une leucinose.

INTRODUCTION: Clinical pictures resembling acrodermatitis enteropathica have been described in acquired zinc deficiency and deficiencies of other nutrients such as biotin, essential fatty acids and amino acids as well as biotin metabolism disorders. We describe the case of an infant with maple syrup urine disease who developed an acrodermatitis-like syndrome due to iatrogenic valine and isoleucine deficiency. CASE-REPORT: A diagnosis of maple syrup urine disease was made in a 5-month-old infant girl with severe neurologic disorders with extremely high levels of the three branched-chain amino acids (leucine, valine and isoleucine) in plasma and urine. Seven days after the start of therapy with a diet excluding these branched-chain amino acids, plasma isoleucine and valine concentrations were low while plasma leucine remained elevated. At the same time, a periorificial and acral dermatitis appeared together with diarrhea. Serum zinc concentrations were normal. A diagnosis of acrodermatitis enteropathica-like syndrome secondary to isoleucine and valine deficiency was suspected. Valine and isoleucine supplementation resulted in rapid resolution of the eruption. DISCUSSION: Several cases of acrodermatitis enteropathica-like eruptions resulting from therapeutic protein restriction diets have been described in infants with different aminoacidopathies. The accompanying dermatosis was associated with a raised plasma leucine/isoleucine ratio and/or isoleucine deficiency, or valine deficiency. While the exact pathogenesis of the skin lesions has not been established, these observations show that branched-chain amino acids are essential for normal growth and differentiation of keratinocytes. The essential role of isoleucine is further substantiated by the fact that its presence is critical in keratinocyte culture media, with growth arrest occurring upon its depletion.

[Thrombosis of legs arteries: imputability of anti-phosphatidylethanolamine antibodies?]. / Thromboses artérielles des membres inférieurs: responsabilité des anticorps antiphosphatidyléthanolamine?

BACKGROUND: At the beginning the antiphospholipid antibodies syndrome was associated with systemic lupus erythematosus. But since 1988 it has become a sole entity. Its current definition is based on the criteria established in 1999 by Sapporo and consists of associating the clinical criteria of thrombosis of arteries or peripheral veins and of miscarriage of pregnancy with the biological criteria. Either anti-cardiolipin antibodies or lupus anticoagulant must be present. Anti-phosphatidylethanolamine antibodies are not included in the Sapporo criteria. CASE REPORT: A non smoking, 43 year-old man showed a clinical manifestation of livedo on the thighs, and left knee and foot, associated with a rapidly extending cutaneous necrosis on the left toes. One year earlier his right leg was amputated up to half of the calf following distal gangrene. The gangrene was consecutive to a stent implantation after a significant stenosis of the right superficial femoral artery. The etiological investigations revealed neither thrombophily nor cholesterol embolism nor vasculitis. No sign of underlying neoplasia could be found. These clinical symptoms as well as the anamnesis were strongly suggestive of an antiphospholipid antibodies syndrome. The immunological dosages revealed isolated positive anti-phosphatidylethanolamine antibodies, persistent six weeks later. DISCUSSION: Several cases of clinical manifestations of the antiphospholipid antibodies syndrome have been described, without any anti-cardiolipin antibodies or lupus anticoagulant, but with presence of anti-phosphatidylethanolamine antibodies. In cases of these strong evocative symptoms but no evidence of the classical biological Sapporo criteria, these antibodies should be systematically searched for.

Modulation of exogenous and endogenous levels of thioredoxin in human skin fibroblasts prevents DNA damaging effect of ultraviolet A radiation.

Thioredoxin (Trx) plays important biological roles both intra- and extracellularly via thiol redox control. We have previously demonstrated that Trx exhibited protective effects against UVA cytotoxicity in human skin fibroblasts. As an extension of the latter investigation, the present work is aimed at assessing ability of Trx to maintain genomic integrity in human skin fibroblasts upon exposure to UVA radiation. Indeed, UVA (320--380 nm) is mutagenic and induces genomic damage to skin cells. The alkaline comet assay was used in association with DNA repair enzyme including formamido pyrimidine glycosylase (Fpg) and endonuclease III (endo III) to estimate the amount of modified bases together with the level of strand breaks and alkali-labile sites. The HPLC-EC assay was applied to assess 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels and to permit the calibration of comet assay as previously described. We reported that overexpression of human Trx (transient transfection) as well as exogenous human recombinant Trx added to the culture medium, decreased the level of DNA damage in UVA irradiated cells. Interestingly, transfection appeared to prevent UVA-induced 8-oxodGuo (3.06 au per Joules.cm(-2) compared to 4.94 au per Joules.cm(-2) for nontransfected cells). Moreover, Trx accumulates into nuclei in transfected cells. This finding supports the notion that Trx is important for the maintenance of the integrity of genetic information. This work demonstrated that under conditions of UVA oxidative stress, Trx prevented the UVA-induced DNA damage.

Induction of thioredoxin by ultraviolet-A radiation prevents oxidative-mediated cell death in human skin fibroblasts.

The present study analyzes the expression of the thioredoxin/thioredoxin reductase (Trx/TR) system in UVA-irradiated human skin fibroblasts. Irradiation increases the intracellular level of Trx and a time-dependent increase of Trx mRNA is observed. Our data indicate that Trx translocates from the cytoplasm to the nucleus. In addition, UV exposure results in an increase in TR synthesis. In order to evaluate the function of Trx/TR system, we investigated the antioxidant role of Trx in transient transfected cells. The ROS accumulation in UVA irradiated cells was assessed using flow cytometry. A 3-fold decrease in ROS production was observed in transiently transfected fibroblasts. These results indicate that Trx acts as an antioxidant protein in UVA irradiated fibroblasts. As ROS are inducers of cell death, this raises the question as to whether Trx is able to protect cells from apoptosis and/or necrosis induced by UVA. Six hours after UVA-irradiation, 29.92% of cells were annexin-V positive. This population was significantly reduced in Trx-transfected cells (8.58%). Moreover, this work demonstrates that Trx prevents the loss of the membrane potential of the mitochondria, the depletion of cellular ATP content, and the loss of cell viability induced by irradiation.

[Problems posed by the therapeutic use of photosensitizers in dermatology]. / Problèmes posés par l'utilisation thérapeutique des photosensibilisateurs en dermatologie.

Three phototherapeutic regimens with photosensitization are now used in dermatology: PUVA (psoralen + UVA), TUV (crude coaltar + UV), PRT (phototherapy with hematoporphyrin derivative). The efficiency of PUVA and TUV is well known in several dermatoses. PRT is now being tested experimentally. For TUV, the lack of a standardized regimen does not allow a clear-cut evaluation of the therapy. For PUVA, late side-effects, particularly carcinogenicity have to be considered. To improve efficiency and minimize the side-effects of PUVA some procedures, such as association with retinoïds, pharmaco-kinetic studies for individual adaptation of the therapeutic regimen and the use of new less mutagenic psoralens are helpful. The persistent phototoxicity following treatments with hematoporphyrin derivative constitutes the major side-effect observed, for this phototherapy.

Protective effects of antioxidants against UVA-induced DNA damage in human skin fibroblasts in culture.

Ultraviolet A radiation (UVA, 320-400 nm) is mutagenic and induces genomic damage to skin cells. N-acetyl-cysteine (NAC), selenium and zinc have been shown to have antioxidant properties and to exhibit protective effects against UVA cytotoxicity. The present work attempts to delineate the effect of these compounds on genomic integrity of human skin fibroblasts exposed to UVA radiation using the single cell gel electrophoresis (SCGE) or Comet assay. The cells were incubated with NAC (5 mM), sodium selenite (0.6 microM) or zinc chloride (100 microM). Then cells were embedded in low melting point agarose, and immediately submitted to UVA fluences ranging from 1 to 6J/cm2. In the Comet assay, the tail moment increased by 45% (1 J/cm2) to 89% (6J/cm2) in non-supplemented cells (p)<0.01). DNA damage was significantly prevented by NAC, Se and Zn, with a similar efficiency from 1 to 4J/cm2 (p < 0.05). For the highest UVA dose (6J/cm2), Se and Zn were more effective than NAC (p < 0.01).

Does manganese protect cultured human skin fibroblasts against oxidative injury by UVA, dithranol and hydrogen peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H2O2 cytotoxicity.

Protective effect of selenium and zinc on UV-A damage in human skin fibroblasts.

Ultraviolet A radiation participates in cytotoxicity and carcinogenesis of the skin by a mechanism involving the generation of reactive oxygen species. Endogenous antiradical defense systems utilize metalloenzymes including Se-dependent glutathione peroxidase and Cu and Zn superoxide dismutase. The aim of the present work was to determine the protective effect of two trace elements, Se and Zn, on cultured human diploid fibroblasts exposed to UV-A radiation (broad-spectrum source with a maximum intensity at 375 nm). Selenium in the culture medium (0.1 mg/L) in the form of sodium selenite increased the synthesis and activity of glutathione peroxidase by 60.5% in the absence of exposure to UV-A radiation and by 35% after irradiation with 5 J/cm2 (P = 0.043). The presence of this element significantly increased the survival of UV-A-irradiated fibroblasts (P < 0.0001). This confirms the essential role of Se in the detoxifying activity of the enzyme. In addition, thiobarbituric acid-reacting substances (TBAR), which are lipid peroxidation markers, decreased in the presence of exogenous Se: -19% and -22% without irradiation and after irradiation with 5 J/cm2 (P = 0.056). When Zn was added at the dose of 6.5 mg/L as ZnCl2, fibroblasts subjected to oxidizing stress induced by UV-A were protected from cytotoxicity (P < 0.0001). The TBAR production decreased significantly: -33% without irradiation and -34% after irradiation with 5 J/cm2 (P = 0.008). Superoxide dismutase activity, however, decreased after supplementing with Zn: -26% without irradiation and -20% after UV-A irradiation (P = 0.017). The antioxidant properties of Zn are thus apparently independent of superoxide dismutase activity.

UV-A1 cytotoxicity and antioxidant defence in keratinocytes and fibroblasts.

The levels of antioxidant molecules and lipid peroxidation, under basal conditions, were measured in normal, human cutaneous keratinocytes and fibroblasts. Total glutathione, glutathione peroxidase and superoxide dismutases are significantly higher in normal keratinocytes compared to normal fibroblasts (respectively +248%, +193% and +155%). Under the same conditions, lipid peroxidation is significantly lower in basal keratinocytes compared to fibroblasts. UV-A1 cytotoxicity was investigated in both cutaneous cell types showing that diploid keratinocytes are more resistant to UV-A1 oxidative stress than fibroblasts (by a factor of around 8). We studied the same parameters in two keratinocyte cell lines, NCTC2544 and HaCaT cells, and in MRC5 fibroblasts. Antioxidant content and lipid peroxidation under basal conditions are quite different in these cell lines compared to those of the normal corresponding cells. Furthermore, NCTC2544 keratinocytes are more sensitive to UV-A1 radiation than normal keratinocytes whereas HaCaT keratinocytes are more resistant, and MRC5 fibroblasts are more resistant than normal cutaneous fibroblasts. These findings suggest that (i) cultured epidermal and dermal cells have different sensitivities to UV-A1 radiation that may be linked to different antioxidant capacities and (ii) cell line response to UV-A1 radiation may differ from that of normal cells.