SUPPRESSION OF THE INDUCTION OF DELAYED-TYPE HYPERSENSITIVITY REACTIONS IN MICE BY A SINGLE EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— After a single exposure of mice to UV radiation, their ability to generate a contact hypersensitivity (CHS) response to contact sensitizers applied epicutaneously to distant, unirradiated skin is severely impaired. It is not clear, however, if the classic delayed type hypersensitivity (DTH) reponse to exogenous antigens, injected into the subcutaneous (s.c.) space, can also be modulated by UV radiation. We report here that a single exposure of mice to UV radiation suppressed the induction of DTH to both erythrocyte and soluble protein antigens injected s.c., but did not suppress the elicitation of the response. The suppressive effect was abrogated by cyclophosphamide treatment. In addition, antigen-specific suppressor cells were found in the spleens of the mice with a decreased DTH response. Since the ability to mount a DTH response has been linked with the resistance to certain pathogenic microorganisms, we suggest that the suppression of DTH by UV radiation may have the potential to compromise host resistance to such infectious agents.     

INDUCTION OF SKIN TUMORS IN HAIRLESS MICE BY A SINGLE EXPOSURE TO UV RADIATION*

Abstract— Skin tumors were induced in hairless mutant mice following a single exposure to ultraviolet radiation (UV). Tumors were first noted as early as 7 weeks following irradiation. The UV, emitted by FS20/40T12 fluorescent lamps, was principally in the 280–320 nm spectral region with a peak at 313 nm. Single (skin surface) doses of 3 times 10⁴ J/m² to 24 times 10⁴ J/m² were delivered in 3 h or less. The higher doses resulted in more severe acute damage as well as greater tumor yield. Most of the tumors were benign hyperplastic epithelial papillomas; 4 out of 96 tumors examined histologically proved to be squamous cell carcinomas. This appears to be the first report of experimental carcinogenesis due to a single UV exposure, not requiring exogenous chemical promotion.     

LOCAL SUPPRESSION OF CONTACT HYPERSENSITIVITY IN MICE BY A MONOFUNCTIONAL PSORALEN PLUS UVA RADIATION

Monofunctional psoralens, plus UVA radiation are not erythemogenic and are less mutagenic than bifunctional psoralens plus UVA radiation. Thus, they have received considerable attention in recent years as potential therapeutic agents for various skin diseases. The purpose of this study was to examine the immunologic side effects following treatment of mice with a monofunctional psoralen plus UVA radiation. We report that angelicin plus UVA radiation suppressed the induction of contact hypersensitivity to dinitrofluorobenzene. This decreased immune response was associated with the presence of splenic suppressor cells that transferred suppression to normal recipients. Treatment with angelicin and UVA radiation also decreased the number of Thy-1+ and Ia+ dendritic epidermal cells in the treated site. We conclude that although this monofunctional psoralen is not phototoxic, it has immunosuppressive activity in mice.     

EFFECT OF UV IRRADIATION ON LETHAL INFECTION OF MICE WITH Candida albicans

Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m² UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicuns in the kidneys, in contrast to sensitized, unirradiated mice. The induction of cutaneous inflammation with turpentine had no effect on the survival rate of mice lethally infected with C. albicans, suggesting that inflammation alone is not sufficient to decrease the survival time of C. albicans-infected mice.     

A DOSIMETRIC TECHNIQUE FOR THE MEASUREMENT OF ULTRAVIOLET RADIATION EXPOSURE TO PLANTS

Abstract Due to the effects of geometry, orientation, atmospheric conditions and optical properties of leaves and soils, the UV exposure to a plant may differ significantly from that of ambient radiation. This paper presents a method utilizing a passive measuring technique with polysulfone dosimeters that provides the ability of measuring the UV exposure at a number of sites simultaneously. The UV exposures are measured at selected sites over models of three canopy shapes with a computer program interpolating and summing these to provide the total UV exposure incident on the canopy.     

INHIBITION OF THE IMMUNE RESPONSE TO ALLOANTIGEN IN THE RAT BY EXPOSURE TO ULTRAVIOLET RADIATION

Exposure of mice to ultraviolet radiation (UV) followed by alloantigen sensitization can suppress the immune response to that alloantigen. In order to assess the applicability of using UV-induced immunosuppression in organ transplantation, the effectiveness of UV in prolonging the survival of vascularized organ allografts must be determined. Because, for technical reasons, rats are better suited than mice for such experiments, we first wanted to determine whether UV suppresses the immune response of inbred rats to alloantigens. The data presented here demonstrate that exposure of rats to UV (115-129 kJ/m2) prior to alloantigenic sensitization decreases the mixed lymphocyte response to alloantigen. The depression of the proliferative response to alloantigen was selective in that spleen cells from the UV-treated rats could respond to mitogenic stimulation. In contrast to previous results with mice, suppressor cells could not be demonstrated in the spleens of the UV-treated rats. In addition, UV treatment after sensitization inhibited the response to alloantigen. These data suggest that treatment of the recipient with UV before or after alloantigenic sensitization may provide a novel method of inhibiting immune responses to allogeneic antigens.     

UROCANIC ACID ANALOGUES AND THE SUPPRESSION OF THE DELAYED TYPE HYPERSENSITIVITY RESPONSE TO Herpes simplex VIRUS

Ultraviolet irradiated urocanic acid (4-imidazoleacrylic acid) containing a mixture of cis- and trans-isomers has been shown previously to induce suppression of the delayed type hypersensitivity (DTH) response to Herpes simplex virus type 1 (HSV-1) in a murine model of infection. The cis-isomer of urocanic acid was prepared and the cis- and trans-isomers of 2-methylurocanic acid. 2-pyrroleacrylic acid, 2-furanacrylic acid, 2-thiopheneacrylic acid, 3-thiopheneacrylic acid as well as dihydrourocanic acid and histamine. Each was applied at concentrations of 1 and 50 micrograms per mouse to the shaved dorsal skin and the mice were infected subcutaneously with HSV 5 h later. After 8-10 days the DTH response to the virus was measured by an ear swelling test. It was found that cis-urocanic acid was effective in suppressing the DTH response at levels of 1 microgram per mouse or less. The cis- and trans-isomers of 2-furanacrylic acid, 2-pyrroleacrylic acid and 2-thiopheneacrylic acid were also effective, with the cis- form generally being more active than trans, and 2-pyrroleacrylic acid being particularly potent. Cis- and trans-3-thiopheneacrylic acid, on the other hand, were only marginally immunosuppressive while neither isomer of 2-methylurocanic acid had any suppressive ability. Dihydrourocanic acid and histamine were also shown to suppress the DTH response. Thus the structural features necessary for urocanic acid and its analogues to act as mediators of UV-induced immunosuppression could be deduced and implications for their mechanism of action discussed.     

SUPPRESSION OF CONTACT HYPERSENSITIVITY BY UV RADIATION AND ITS RELATIONSHIP TO UV-INDUCED SUPPRESSION OF TUMOR IMMUNITY

Abstract— In this study, we examine some of the photobiologic and immunologic characteristics of the suppression of contact hypersensitivity (CHS) by UV radiation. BALB/c mice were irradiated on the shaved dorsal skin with FS40 sunlamps and sensitized 5 days later by applying a contact sensitizer lo the shaved abdomen. The suppression of CHS resulting from exposure to a given total dose of UV radiation was unaffected by changes in dose fractionation over a 5-day period and by changes in dose-rate over a 10-fold range. Elimination of wavelengths below 315 nm with a mylar filter abrogated the suppressive effect of the sunlamps, even when the same total energy was administered. Irradiation of unshaved mice required 14 times more energy to produce 50% suppression than was required for shaved mice, suggesting that the exposed skin is the primary target of this effect. Contact sensitization of UV-irradiated, but not unirradiated, mice induced the appearance of antigen-specific suppressor T lymphocytes in their spleen. The photobiologic and immunologic similarities between the suppression of CHS by UV radiation and the UV-mediated suppression of tumor rejection that we described previously suggest that these two immunosuppressive effects of UV exposure share certain steps in their pathways.     

INDUCTION OF SKIN TUMORS IN THE RAT BY SINGLE EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— The dose response for tumor induction in albino rat skin by single exposures of UV radiation has been characterized. The shaved dorsal skin of 202 animals was exposed to either of two sources: one emitting a broad spectrum of wavelengths from 275 to 375 nm, and the other emitting at 254 nm. Skin tumors began to appear within 10 weeks of exposure and continued to appear for 70 weeks. The highest tumor yield was 5.5 tumors per rat and occurred when the rats were exposed to 13.0 times 10⁴ J/m² of the 275–375 nm UV. The 275–375 nm UV was about eight times as effective as the 254 nm UV for the induction of tumors throughout the exposure range from 0.8 times 10⁴ to 26.0 times 10⁴J/m². Tissue destruction and hair follicle damage was found at the highest exposure to 275–375 nm UV but at none of the exposures to 254 nm UV. Repeated weekly exposures to 275–375 nm UV proved less effective than an equivalent single exposure for inducing tumors, even though the multiple exposures caused more severe skin damage. The transmission of the UV through excised samples of rat epidermis indicated that the exposure to the basal cell layer was about 3% of the surface exposure at 254 nm and about 15% of the surface exposure between 275 and 320 nm. The dependence of tumor yield on UV exposure was linear for 254 nm UV but was more complex for the 275–375 nm UV. For the latter more tumors were produced per unit exposure at lower exposures than at higher exposures.     

SENSITIVITY OF MARINE PHYTOPLANKTON TO UV-B RADIATION: IMPACT UPON A MODEL ECOSYSTEM

Abstract Human activities may cause a 16% reduction of stratospheric ozone. The concomitant increase in solar UV-B radiation reaching the surface of the earth could detrimentally affect the phytoplankton that form the base of the food web in oceanic and estuarine ecosystems. In the current study acute exposure of seven species of marine phytoplankton to UV–B radiation depressed the radiocarbon estimate of primary production. A model of a marine ecosystem was constructed based on the differential sensitivities of the seven species of phytoplankton. Increasing the UV–B exposure within the model from 100 Eff_DNAJ/m²/day to 150 Eff_DNAJ/m²/day significantly altered the community composition of the ecosystem. In nature, alteration of the phytoplanktonic community structure could result in a significant impact upon successional patterns and primary producer–consumer trophodynamics.     

ENHANCEMENT OF INTRINSIC ANTITUMOR ACTIVITY IN SPORE-ENDOTOXIN MIXTURES OF Bacillus thuringiensis BY EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— Irradiation of spore-endotoxin mixtures from Bacillus thuringiensis cultures at 254 nm (60 μW cm^-2) enhances their intrinsic antitumor potency as well as that of either component. The extent of enhancement depends on the length of exposure (optimum: 35 min) and may thus be due to photochemical changes of the endotoxin protein or/and to photoproduction of additional compounds with antitumor activity. Antitumor effects, expressed as survival rates of C57BL/6 mice inoculated with Lewis' mouse lung carcinoma and subjected to treatments 24 h later, depended on the number of doses of preparations administered (mixture, separated components).     

IMPACT OF UV-B RADIATION UPON ESTUARINE MICROCOSMS

Abstract— Twelve flow-through estuarine microcosms were exposed daily to four different levels of UV-B radiation (290–320. nm)(1.57 ± 10², 6.43 ± 10³, 6.86 ± 10³ and 7.61 ± 10³ J·m_-2d⁻¹) in addition to a natural level of visible solar radiation (380-800. nm). The parameters studied over a four week period were phytoplankton community composition, plankton biomass (ash-free dry weight), chlorophyll a concentration and primary productivity (radiocarbon uptake). With increased exposure to UV-B radiation there was an obvious alteration of the community composition. Daily exposure to enhanced levels of UV-B radiation also depressed the biomass, the chlorophyll a concentration and the radiocarbon uptake of samples from the ecosystems.     

SKIN DAMAGE IN ADULT AMPHIBIANS AFTER CHRONIC EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— The effects of repeated UV exposure on the skin of the European crested newt, Triturus cristatus carnifex , have been investigated. The animals were irradiated 3 times per week with a Westing-house FS40T12 fluorescent sun lamp (wavelength spectrum 275–350 nm). Two groups of animals received the same total fluence of 1.3 × 10⁵ J/m² in single fluences of either 1570 J/m² (group A) or 9430 J/m² (group C), and one group received a total fluence of 2.6 × 10⁵ J/m² in single fluences of 4710 J/m² (group B). All the animals were killed 7 months after the first UV exposure, but at different intervals after the last exposure. Striking epidermal hyperplasia was found in the newts irradiated at the lower fluence rate (group A). In the animals given the higher total fluence (group B), the most prominent skin changes were dermal fibrosis and irregular thinning and thickening of the epidermis. No significant skin changes were found in group C., in which if there had been UV lesions, they had been repaired during the 5 month interval between the last irradiation and the killing of the animals. No skin tumors developed in any experimental group.     

THE OCULAR DOSE OF ULTRAVIOLET RADIATION FROM SUNLIGHT EXPOSURE

Abstract— The ocular toxicity of ultraviolet radiation has been demonstrated in acute photokeratitis and is suspected of contributing to cataractogenesis and senile macular degeneration. While previous studies have emphasized photochemical and epidemiologic aspects of ocular UV-B irradiation, little is known about the extent of such exposure in human subjects. To determine levels of ocular UV-B exposure from sunlight, four mannikin headforms were fitted with UV-B sensitive film (polysulphone) and exposed on an unobstructed rooftop (Baltimore, Md.: latitude = 39.5 degrees) to four hours of sunlight (11 am-3 pm local time) over a three month period (June-August). Simultaneous measurements of ocular and ambient exposure revealed a ratio of 19.5 ± 2.9% that was independent of ambient level (P < 0.05). Measurements performed during earlier hours (8 am-11 am) revealed a similar ratio. Mannikin headforms fitted with brimmed baseball caps showed a22–95% reduction in ocular exposure, depending on the angle of the hat brim to the forehead. Three sets of spectacles substantially reduced ocular UV-B exposure,62–94% dependent on the absorption properties of the spectacle lenses. These anthropomorphic measurements indicate that a substantial percentage of ambient UV-B light is incident upon the cornea and that personal factors, such as wearing a hat or spectacles, can markedly affect UV-B exposure.     

EXPOSURE TO LONG WAVELENGTH ULTRAVIOLET RADIATION DECREASES PROCESSING OF LOW DENSITY LIPOPROTEIN BY CULTURED HUMAN FIBROBLASTS

Exposure of MRC5 human fibroblasts to UVA radiation (365 nm) resulted in a dose-dependent decrease in low density lipoprotein (LDL) uptake and degradation by cells. Following a 25 J/cm² irradiation dose, about 45% and 70% reduction in ¹²⁵I-LDL uptake and degradation were observed, respectively. Under the same conditions, the ¹⁴C-sucrose uptake was also decreased to about the same extent as LDL uptake. Cell pretreatment with the antioxidants vitamin E and vitamin C did not prevent the UVA-induced fall in LDL degradation. These results point to the possible effects of UVA radiation on receptor-mediated and nonspecific uptake of exogenous molecules. With special regard to the alterations in receptor-mediated processing of exogenous ligands, such a phenomenon could be of importance in UVA-induced skin degenerative processes.     

几种螯合剂解镍致小鼠急性肾毒性作用比较

为寻找镍(Ni)新型解毒剂，小鼠腹腔注射氯化镍溶液(5 mg Ni/kg)，观察二乙氨基二硫代甲酸钠(DDTC)，二羟乙氨基二硫代甲酸钠(DHED)，N-苯甲基-D-葡糖氨基二硫代甲酸钠(BGD)，meso-2，3-二巯基丁二酸钠(DMSA)及环己烷二胺四乙酸钠(CDTA)等螯合剂对镍致小鼠肾脏毒性的解毒作用。镍染毒引起小鼠肾脏脂质过氧化(LPO)和钙、铁及锌浓度增加，血清肌酐及血液尿素氮(BUN)升高。镍染毒30分钟和24小时后进行各螯合剂治疗(剂量均为400 μmol/kg     

EFFECT OF UV RADIATION ON SURVIVAL OF NON-HAIRED MICE

Abstract— Patterns of mortality in a series of photocarcinogenesis experiments were examined. All experiments involved chronic irradiation of genetically non-haired mice with simulated sunlight from a Xe lamp. Experimental variables included genetic origin of the test animals, incident dose of radiation, and the spectral quality of the radiation. In 16 experiments involving 10 genetic origins of mice the following patterns were detected: (1) survival was inversely proportional to the delivered radiation dose; (2) within origins the life-shortening efficacy of radiation was closely correlated with its carcinogenic efficacy; (3) between genetic origins the carcinogenicity and lethality of a radiation dose were qualitatively correlated, but relative efficacy for the two effects varied; (4) altering the source spectrum by modifying the short-wave (UVB) cutoff produced similar changes in carcinogenicity and lethality, suggesting that UVB was a significant contributor to lethal efficacy; (5) nature and relative timing of the carcinogenic response were such that carcinogenesis was not likely to have caused the observed mortality. It is speculated that systemic effects, possibly immunologic or toxic, are produced by chronic UV irradiation, and that these apparently cumulative, dose-dependent effects result in premature death of non-haired mice.     

EFFECTS OF in vitro EXPOSURE TO ULTRAVIOLET RADIATION ON THE FUNCTIONAL ACTIVITY OF LYMPHOCYTES, WITH EMPHASIS ON SUSCEPTIBILITY OF DIFFERENT SPECIES

Abstract In this study lymphocytes from blood and/or spleen of different species (rat, mouse, human) were exposed to different doses of ultraviolet radiation (UVR). The functional activity of these lymphocytes was determined using assays for mitogen proliferation and the mixed lymphocyte response (MLR). These experiments demonstrated that in vitro exposure to UVR causes a dose-dependent decrease of the MLR activity of the irradiated lymphocytes. Viability of lymphocytes and mitogen proliferation responses were also decreased by UVR exposure but less severe in comparison to the MLR. Lymphocytes of rats seem to be more sensitive to UVR as compared to lymphocytes of mice and humans.     

EFFECT OF CHRONIC UV EXPOSURE ON EPIDERMAL TRANSMISSION IN MICE*

In connection with an investigation on UV-tumorigenesis in hairless mice, the question arose in what way the epidermal transmission changes under chronic UV exposure. At regular time intervals, epidermal sheets of these mice were optically probed, i.e. the specimen was irradiated perpendicularly to its surface with a collimated monochromatic beam of 313, 302 or 297 nm and the transmission was measured in forward direction and a small angle around it. The optical probe measurement was sensitive to epidermal changes and easy to perform; it correlated well with thickness and total transmission of the epidermal sheet. As a result it was found that over the dose range investigated the logarithm of the epidermal transmission at 297 nm was a simple linear function of the daily UV dose and the time of treatment. Calculations, in which this result is combined with data on UV-tumorigenesis over the same dose range, show that the change in epidermal transmission is sufficiently large to have an important bearing on the dose-response relationship for tumorigenesis by chronic UV exposure.     

THE EFFECT OF CHRONIC LOW-DOSE UVB RADIATION ON LANGERHANS CELLS, SUNBURN CELLS, UROCANIC ACID ISOMERS, CONTACT HYPERSENSITIVITY and SERUM IMMUNOGLOBULINS IN MICE

Abstract— C3H mice were irradiated three times a week for up to 6 weeks with either 500 J/m² or 1000 J/m² broadband UVB (270–350 nm) or 3000 J/m² narrowband UVB (311–312 nm; TL01 source). Each dose was suberythemal to the mouse strain used. The number of Langerhans cells (LC) in the epidermis was reduced by over 50% after 2 weeks of irradiation with the UVB source and by 20% following TL01 irradiation. Continued irradiation for up to 6 weeks resulted in no further decrease in LC numbers in the case of the UVB source but a steady decline to 40% in the case of the TL01 source. Sunburn cells were detected following irradiation with both sources but the numbers were very low in comparison with acute exposure. Ultraviolet-B exposure resulted in doubling of the thickness of the epidermis throughout the 6 weeks of irradiation while TL01 exposure did not alter epidermal thickness. Conversion of trans- to ew-urocanic acid (UCA) was observed with both UVB and TL01 sources. The percentage of cis -UCA started to return to normal after 4 weeks of TL01 exposure despite continued irradiation. As observed following a single exposure, the contact hypersensitivity (CH) response was significantly reduced following 6 weeks of UVB irradiation but was unaffected by TL01 exposure, indicating no correlation between cis -UCA levels and CH response. Total serum immunoglobulin levels remained unchanged throughout the 6 weeks of UVB or TL01 irradiation but IgE titers significantly increased in all cases in the first 2 weeks of irradiation, indicating a possible shift to a T_H2 cytokine profile. The IgE levels started to return to normal at later times. Thus chronic broadband UVB exposure induces a number of cutaneous and systemic responses that are likely to be dose dependent, while chronic TL0I exposure induces only some of the these responses.