Acute effect of 8-methoxypsoralen and ultraviolet light on sister chromatid exchange

Summary The acute effect of 8-methoxypsoralen (8-MOP) and 8-MOP+long wave ultraviolet light (UVA) on sister chromatid exchange (SCE) has been examined in an in vitro experiment. The SCE count was significantly increased by 8-MOP without light, but the effect was substantially greater (50%) by 8-MOP+UVA. In addition, mitoses with banded staining of the chromosomes were seen after 8-MOP and UVA. These changes were dose dependent, and they might be responsible for the reduced cell turnover in psoriasis plaque after PUVA.     

Environmental wavelengths of ultraviolet light induce cytoskeletal damage

The ultraviolet component of sunlight is the major cause of skin cancer and is responsible for accelerating the aging of human skin. It is therefore important to determine the mechanisms by which ultraviolet light alters normal cellular functions. The potential importance of ultraviolet light-induced damage to non-DNA targets has received little attention. Since the cytoskeleton is an important participant in the control of normal cell growth, the microfilaments and microtubules of UV irradiated human skin fibroblasts have been studied using fluorescence microscopy. Polychromatic ultraviolet light, composed of environmentally relevant wavelengths, was found to disrupt the cytoplasmic microtubule complex in a dose dependent manner. The induction of microtubule disassembly did not correlate with the cytotoxicity of ultraviolet light of varying composition.     

Topical calcitriol is degraded by ultraviolet light

Calcitriol ointment has been approved for the treatment of psoriasis in many countries around the world. It may be prescribed in conjunction with phototherapy. Our purpose was to evaluate the effect of various therapeutic ultraviolet modalities on the stability of calcitriol and, conversely, to study the effects of calcitriol ointment on transmission of different forms of ultraviolet light. Calcitriol ointment 3 microg per g was irradiated with 10 J per cm2 ultraviolet A, 100 mJ per cm2 broadband ultraviolet B, and 3.0 J per cm2 narrowband ultraviolet B, and its stability was compared with samples exposed to fluorescent light and ambient sunlight. Ultraviolet A and ultraviolet B transmission were measured through thin and thick layers of calcitriol 3 microg per g ointment and vehicle. More than 90% of calcitriol ointment is degraded upon exposure to ultraviolet A, broadband ultraviolet B, and narrowband ultraviolet B. Transmission of ultraviolet A is reduced through calcitriol ointment and its vehicle by 17%-31% and 17%-41%, respectively. Transmission of ultraviolet B is reduced by 67%-87% through vehicle and 50%-83% through calcitriol ointment. When used in conjunction with phototherapy, calcitriol ointment should be applied after ultraviolet exposure, not before. Calcipotriene, the only vitamin D analog already approved for psoriasis in the USA, has been used successfully in combination with ultraviolet B and psoralen plus ultraviolet A.     

Effect of long-wave ultraviolet light (UV-A) and medium-wave ultraviolet rays (UV-B) on human skin. Critical comparison

When discussing the effects of ultraviolet radiation on human skin, one should carefully distinguish between the long wave ultraviolet light (UV-A) and the short wave radiations (UV-B and UV-C). Ultraviolet A induces immediate pigmentation but, if high energies are applied, a permanent pigmentation is elicited. This type of ultraviolet A-induced pigmentation has been called "spontaneous" pigmentation as no erythematous reaction is necessary to induce or accelerate melanine formation. Ultraviolet B provokes erythema and consecutive pigmentation. Upon chronic exposure, ultraviolet B causes the wellknown actinic damage of the skin and even provokes carcinoma. With exposures to the sunlight (global radiation), one should be most careful. The public must be informed extensively about the dangers of excessive sunbaths. The use of artificial "suns" with spectra between 260 and 400 nm is limited as it may cause the same type of damage as the global radiation. An exact schedule for use of artificial lamps is strongly recommended. After one cycle of exposures, an interruption is necessary until the next cycle of irradiations may start. Upon continual use for tanning of the skin, artificial lamps may provoke irreversible damage of the skin. Radiation sources with emission spectra of wavelengths between 315 and 400 nm exclusively are well suited for the induction of skin pigmentation (cosmetic use). Potent radiation such as UVASUN systems provoke a "pleasant" permanent pigmentation after exposures for less than one hour. The use of ultraviolet A (UV-A) does not carry any risk for the human skin.     

Protection from visible light by commonly used textiles is not predicted by ultraviolet protection

Interest is increasing in the prevention of acute and chronic actinic damage provided by clothing. This interest has focused mainly on protection against ultraviolet irradiation, but it has now also turned to protection against visible light. This change is mainly due to the action spectrum in the visible light range of some photodermatoses and the increasing interest in photodynamic therapy. The ultraviolet protection provided by commercially available textiles can be graded by determining an ultraviolet protection factor. Several methods have already been used to determine the ultraviolet protection factor. The fact that protection from visible light by textiles cannot be predicted by their ultraviolet protection makes the situation more complicated. This study attempts to determine whether or not the ultraviolet protection factor value of a particular textile is a good parameter for gauging its protection in the visible light range and concludes that a protection factor of textile materials against visible light needs to be developed. This development should go beyond the protection factor definition used in this article, which has some limitations, and should take into account the exact action spectrum for which the protection is needed.     

The development of a filter to enhance the efficacy and safety of excimer light (308 nm) therapy

Background: Excimer light (308 nm) therapy is a new ultraviolet (UV) B phototherapy for which the efficacy and resulting DNA damage are not well established.
Purpose: To develop an effective and safe phototherapy using the excimer lamp, we studied the effects of different light cut-off filters, A and B.
Methods: Efficacy was evaluated by measuring apoptosis using fluorescence-activated cell sorting analysis. DNA damage was evaluated by measuring cyclobutane pyrimidine dimers (CPDs). Light sources, including normal wave and short wave (SW) excimer light, broad-band (BB) UVB, and narrow-band (NB) UVB, were examined using the filters. A human skin equivalent model was also examined.
Results: The ratio of positive apoptosis to CPD formation normalized to the mean induced by NB-UVB was 5.7 using the excimer lamp without a filter, 6.3 using the excimer lamp with the A filter, 6.4 using the SW excimer lamp without a filter, and 4.2 using the BB-UVB. The A filter reduced CPD formation induced by the normal wave and SW excimer lamp. In the human skin equivalent model, the use of filters significantly decreased the amount of CPD-positive cells.
Conclusions: These findings suggest that using the A filter with the excimer lamp increases the efficacy and safety of excimer light therapy.     

Suppression of epidermal proliferation by ultraviolet light, coal tar and anthralin

360 nm ultraviolet light (UVA) plus coal tar depresses mitosis and DNA synthesis in epidermal cells. UVA has no effect by itself. In some models coal tar alone can partially depress DNA synthesis. 254 nm ultraviolet light (UVC) and 290--320 nm ultraviolet light (UVB) do not enhance depression of DNA synthesis by coal tar. Dithranol will suppress mitosis and DNA synthesis of epidermal cells but there appears to be no photo-activation by UVA. Dithranol suppression and suppression of DNA synthesis by UVB or UVC are additive when used together.     

Immune sensitization against epidermal antigens in polymorphous light eruption

To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.     

Evaluation of apoptotic cells induced by ultraviolet light B radiation in epidermal sheets stained by the TUNEL technique

Two major components of epidermal cells, keratinocytes and Langerhans cells, are injured by ultraviolet light B radiation, resulting in sunburn cell (apoptotic cell) formation, impaired function, and a reduced number of Langerhans cells. Quantitative analysis of Langerhans cell damage is usually performed using epidermal sheets, whereas that of keratinocytes has been performed by counting the number of sunburn cells in vertical tissue sections. In this study we assessed the influences of ultraviolet light B radiation on epidermal cells by apoptotic cell formation, using murine epidermal sheets stained by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. Ten to 75 mJ per cm2 of ultraviolet light B radiation induced apoptotic cells in abdominal skin of C3H mice. The cells were induced in 6 h after 50 mJ per cm2 of ultraviolet light B irradiation with the peak in number in 24 h, 18.8 +/- 5.0 per mm2 and 97.7 +/- 7.4 per mm2, respectively. One week later, the apoptotic cells were not visualized. As C3H/He, BALB/C, and C57BL/6 mice showed almost the same frequency of apoptosis in epidermal sheets from 50 mJ per cm2 ultraviolet light B-irradiated skin, the induction of the cells by ultraviolet light B radiation did not depend on the genetic trait of the mouse. Xeroderma pigmentosum type A gene-deficient mice, however, showed a greater induction of apoptotic cells (216.9 +/- 25.2 per mm2) by ultraviolet light B radiation than xeroderma pigmentosum type A wild-type mice (89.5 +/- 13.6 per mm2) and conventional mice. Pretreatment with a SPF 60 sunscreen agent was quite effective in reducing the induction of apoptotic cells. Using confocal laser scanning microscopy and double staining, 1.5 +/- 2.7% of apoptotic cells were Ia-positive cells in 24 h after 50 mJ per cm2 of ultraviolet light B radiation. Apoptotic Ia-positive cells were not observed 48 h after the radiation. On the other hand, no apoptotic dendritic epidermal T cells were observed in up to 75 mJ per cm2 of ultraviolet light B radiated skin. Thus, nearly all apoptotic cells were keratinocytes, and Langerhans cells and dendritic epidermal T cells appeared resistant to ultraviolet light B-induced apoptosis. Compared with the assessment in vertical tissue sections, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique with epidermal sheets appeared to be a more physiologically relevant method for quantitative evaluation of apoptotic epidermal cells induced by ultraviolet light B radiation.     

Prevention of polymorphous light eruption and solar urticaria

Polymorphous light eruption (PLE) and solar urticaria (SU) are two photodermatoses that are induced by ultraviolet radiation and sometimes by visible light. This article will review the various means of preventing PLE and SU with an emphasis on the role of sunscreens.     

Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.     

Polymorphous light eruption

Polymorphous light eruption is the most common photodermatosis, with a prevalence of as high as 10–20% in Western Europe and in the USA. It starts during the second and third decades of life. Although not life-threatening it can severely impair the quality of life, in particular during leisure activities and in outdoors workers. Polymorphous light eruption belongs to the group of so-called idiopathic photodermatoses. This term denotes dermatoses that occur in otherwise healthy individuals from exposure to sunlight or artificial light without the intervention of an exogenous photosensitizing agent. These diseases have two factors in common: they are precipitated by ultraviolet or visible radiation; and their exact pathomechanism remains obscure but is presumably immunologic in nature.     

The evolution of current medical and popular attitudes toward ultraviolet light exposure: part 2

The 1920s and 1930s represented an extraordinary time in the shaping of modern attitudes towards ultraviolet light. Dermatologists and other physicians today are still confronting the effects of changes in social behavior that occurred at this time. The discovery that ultraviolet wavelengths played a role in vitamin D synthesis in the skin ushered in a period of enormous popularity for ultraviolet light exposure. A variety of other medical claims were soon made for ultraviolet radiation, including that it increased resistance to disease. The field of phototherapy rapidly expanded, and its use was employed by proponents for a host of unlikely medical conditions. Exposure to sunlight or ultraviolet lamps was widely promoted as a form of preventive medicine. Home sunlamps gained popularity and were aggressively marketed to the public. A suntan, which had previously achieved limited popularity, now was viewed as de rigueur in the United States and Europe. The role that medical advocacy of ultraviolet light exposure played in initially advancing the practice of sunbathing is not commonly appreciated today. Ironically, public health recommendations of the time were often diametrically opposed to those being made at present, since sunlight exposure is currently recognized as the major preventable cause of cancer of the skin.     

Persistent polymorphous light eruption after ultraviolet A1 phototherapy

Polymorphous light eruption (PMLE) is the most common photodermatosis and is characterized by the development of a pruritic skin eruption within a few hours to days after sun or artificial light exposure. The eruption usually takes up to two weeks to resolve in the absence of further ultraviolet radiation. PMLE has been reported as a side effect of ultraviolet A1 (UVA1) therapy but characteristics of the eruption, especially the duration until resolution after treatment, has not been described. A 37‐year‐old female developed an unusually persistent PMLE that lasted for 5 weeks after completion of UVA1 phototherapy.     

Treatment of psoriasis with long-wave ultraviolet light.

The effect of long-wave ultraviolet light on psoriasis was studied in 10 patients, using the method of paired comparisons. The radiation failed to have any demonstrable effect.     

Cockayne's syndrome fibroblasts have increased sensitivity to ultraviolet light but normal rates of unscheduled DNA synthesis

Cockayne's syndrome is a form of cachectic dwarfism characterized by acute sun sensitivity and numerous other abnormalities of many organ systems. We studied fibroblasts from 9 Cockayne's syndrome patients to determine if their fibroblasts had abnormal post-ultraviolet light colony-forming ability or abnormal ultraviolet light-induced unscheduled DNA synthesis. The fibroblast strains from all the patients had markedly decreased post-ultraviolet light colony-forming ability in comparison with fibroblasts from control donors. Since this increased ultraviolet light sensitivity is propagable in vitro, it may be a manifestation of, or be closely associated with, the inherited genetic defect of this autosomal recessive disease. However, the patients' fibroblasts had normal rates of ultraviolet light-induced unscheduled DNA synthesis. Thus, unlike the UV sensitivity of DNA excision repair-deficient xeroderma pigmentosum strains, the UV sensitivity of Cockayne's syndrome strains is not related to abnormal DNA excision repair, at least to the extent that this repair process is reflected by rates of ultraviolet light-induced unscheduled DNA synthesis.     

Efficacy of 308-nm excimer light for Japanese patients with psoriasis

Ultraviolet irradiation therapy, including psoralen and ultraviolet A therapy and narrow-band ultraviolet B (310–312 nm) therapy, is a widely used and highly efficient treatment modality for psoriasis. Therapy with 308-nm excimer light has been reported to be effective for the treatment of psoriasis vulgaris. To evaluate the efficacy of 308-nm excimer light therapy for Japanese psoriasis patients, seven patients (six men and one woman) with plaque-type psoriasis were treated with 308-nm excimer light at 7–14-day intervals. The Psoriasis Severity Index (PSI) was calculated for individual plaques in order to assess the effectiveness of the therapy. A 74.9% mean improvement in the PSI was observed after 10 treatment sessions. These results suggested that targeted irradiation with 308-nm excimer light leads to rapid and selective improvement in plaque-type psoriatic lesions without unnecessary radiation exposure to the surrounding unaffected skin.     

Cell kinetic studies of the effect of DTIC combined with fluorescent light or UVA irradiation on human melanoma cell line (SEKI, II)

The effectiveness of DTIC (5-(3.3-dimethyl-1-triazeno) imidazole-4-carboxamide) against a human malignant melanoma cell line (SEKI, II) was investigated with the additional use of fluorescent light and long wave ultraviolet irradiation. The cell cycle phase distribution of cultured melanoma cells exposed to DTIC (10 μg/ml, 100 μg/ml) was analyzed by means of flow-cytometry (ICP type 11). The cytostatic effect of DTIC was observed at a concentration higher than 10 μg/ml in standard culture. Remarkable enhancement of the effect of DTIC was observed in both fluorescent light and ultraviolet irradiation. The most prominent change in cell cycle phase occurred in the group treated with DTIC 100 μg/ml with fluorescent light. S phase prolongation was shown in early stages (6, 12 hours), and then G₂M phase accumulation was observed in late stages (48 hours). In ultraviolet irradiation groups, enhancement of the cytocidal effect of DTIC was observed 12 hours after irradiation. The death of all of the cells was observed in the DTIC 10 μg/ml + UVA 3 joules/cm² and the DTIC 100 μg/ml + UVA 1 joule/cm² groups. DTIC with UVA irradiation may be used for the treatment of cutaneous malignant tumors.     

Psoriasis improved by anthracene with near ultraviolet light

Anthracene with near ultraviolet (UV) light (UVA, 320--400 nm) has been shown previously to inhibit epidermal deoxyribonucleic acid (DNA) synthesis and mitosis. This suggested that the combination of anthracene and UVA light could suppress the rapidly proliferating epidermis of psoriasis. In this preliminary clinical study, anthracene plus UVA light improved psoriasis as shown by thinning of plaques and decreased scale in four of five patients, with complete or almost complete clearing in two of these four patients. These findings indicate that anthracene with UVA light might be helpful in the control of psoriasis.     

Anthracene with near ultraviolet light inhibiting epidermal proliferation.

Anthracene plus near ultraviolet (UV) light (UV-A, 320 to 400 nm) suppresses DNA synthesis and mitosis in mouse epidermis. Ultraviolet-A light or anthracene alone does not have any effect. There is no photoactivation of anthracene to enhance depression of DNA synthesis by either UV-B (290 to 320 nm) or UV-C (254 nm) light. While methoxsalen with UV-A light inhibits DNA synthesis, the phototoxic drugs chlorpromazine hydrochloride and demethylchlortetracycline do not. The combination of anthracene plus UV-A light may have therapeutic effectiveness for psoriasis with less potential for photocarcinogenesis than psoralens plus UV-A light.