LACK OF CORRELATION BETWEEN SUPPRESSION OF CONTACT HYPERSENSITIVITY BY UV RADIATION AND PHOTOISOMERIZATION OF EPIDERMAL UROCANIC ACID IN THE HAIRLESS MOUSE

Abstract The immunological consequences of exposure to UVA (320–400 nm) radiation are unclear. This study describes the relationship between the generation of epidermal cis -urocanic acid and the ability to respond to a contact-sensitizing agent, in hairless mice exposed to different UV radiation sources, which incorporate successively greater short-wavelength cutoff by filtration of the radiation from fluorescent UV tubes. Mice were exposed to these radiation sources at doses systematically varying in UVB radiation content but supplying increasing proportions of UVA radiation. All radiation sources were found to generate approximately 35% cis -urocanic acid in the epidermis, thus normalizing the sources for cis -urocanic acid production. However, only those sources richest in short-wavelength UVB resulted in suppression of the systemic contact hypersensitivity response. These sources also induced the greatest erythema reaction, measured as its edema component, in the exposed skin. A strong correlation was thus demonstrated between the induction of edema and the suppression of contact hypersensitivity, but there appeared to be no correlation between the generation of epidermal cis-urocanic acid and suppression of contact hypersensitivity. The sources richest in UVA content did not result in suppression of contact hypersensitivity: furthermore mice previously irradiated with such UVA-rich sources were refractory to the immunosuppressive action of exogenous cis-urocanic acid. A protective effect of the increased UVA content thus appeared to be inhibiting immunosuppression by the available endogenously generated or exogenously applied cⁱs-urocanic acid.     

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.     

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.     

DOSE-RESPONSE CHARACTERISTICS OF IMMUNOLOGIC UNRESPONSIVENESS TO UV-INDUCED TUMORS PRODUCED BY UV IRRADIATION OF MICE

Abstract— Irradiation of mice with unfiltered FS40 sunlamps renders them susceptible to challenge with highly antigenic UV-induced skin tumors. Dose-response studies demonstrated that the susceptibility of mice to tumor challenge was directly proportional to the total dose of UV radiation, and was independent of the manner in which the dose was administered. A fractionated dose was no more effective than the same total dose given as a single treatment in inducing susceptibility to tumor challenge. The effects of even suboptimal doses of UV radiation persisted for as long as 6 months after the UV treatment.     

EXPOSURE OF MICE TO UV-B RADIATION SUPPRESSES DELAYED HYPERSENSITIVITY TO Candida albicans

Groups of mice were exposed to a single dose of UV radiation before or after immunization with Candida albicans. The delayed type hypersensitivity (DTH) response was markedly depressed in all UV-irradiated groups. Exposure of mice to UV radiation before sensitization induced splenic suppressor cells that, upon transfer to normal recipients, impaired the induction of DTH to Candida. In contrast, exposure of mice to UV radiation after sensitization interfered with elicitation of the DTH response, but this suppression was not transferable. These studies demonstrate that immunity to Candida albicans in mice is impaired by exposure to UV radiation and that two separate mechanisms may be involved.     

WAVELENGTH DEPENDENCE AND DOSE-RATE INDEPENDENCE OF UV RADIATION-INDUCED IMMUNOLOGIC UNRESPONSIVENESS OF MICE TO A UV-INDUCED FIBROSARCOMA

Irradiation of BALB/c mice with FS40 sunlamps induces susceptibility to challenge with syngeneic UV-induced fibrosarcomas that otherwise would be rejected immunologically. Plastic filters were used to remove various wavelengths from the radiation source to identify the active waveband. Wavelengths above 315 nm (those transmitted through a mylar filter) were ineffective in producing tumor susceptibility, even when the total amount of energy applied was the same as that emitted by the unfiltered FS40 sunlamps. Removal of wavelengths below 275 nm (with a polystyrene filter) did not reduce the activity of the radiation. Alteration of the dose-rate of the radiation by as much as a factor of 10. by irradiating animals through neutral density filters, did not change the proportion of tumor-susceptible mice, suggesting that there is reciprocity with regard to dose-rate and time of UV exposure. Cell transfer studies were used to test whether similar immunologic mechanisms were responsible for the equal susceptibility to tumor challenge of mice given continuous UV exposure (one 12-h treatment) or fractionated exposures (twelve 1-h treatments). With both treatment regimens, tumor susceptibility could be transferred to X-irradiated recipients with lymphoid cells, provided that sufficient time had elapsed after the single treatment.     

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.     

SENSITIVITY OF MONONUCLEAR CELLS TO UV RADIATION

Abstract—The viability of peripheral blood mononuclear cells, as measured by trypan blue dye exclusion, is decreased by exposure to UV radiation in vitro . The toxicity of the UV radiation is doseand wavelength-dependent; UVC is approximately 10 times more effective than UVB and 10⁵ times more effective than UVA.     

SUPPRESSION OF LIPID PHOTOPEROXIDATION BY QUERCETIN AND ITS GLYCOSIDES IN SPINACH CHLOROPLASTS

Abstract— Quercetin, quercitrin and rutin suppressed lipid photoperoxidation in spinach chloroplasts in the presence of 100 μ M carbonylcyanide m -chlorophenylhydrazone (CCCP) or 100 μ M methyl viologen (MV). Fifty percent inhibition of lipid peroxidation by quercetin was observed between 30 and 50 μ M . Concentrations of quercetin and rutin higher than 100 μ M were required to obtain 50% inhibition. Ouercitrin was more effective than rutin in the suppression of lipid photoperoxidation.
Photooxidation of the flavonols by chloroplasts in the presence of MV was suppressed by superoxide dismutase (SOD) more than 90%, and the rates of the oxidation decreased in order of quercetin, quer citrin and rutin suggesting that the reactivity of the flavonols with O₂-decreased in that order. The photooxidation of the flavonols by CCCP-poisoned chloroplasts was partially suppressed by SOD. Radicals generated in the course of lauroyl peroxide degradation also oxidized the flavonols and the oxidation was insensitive to SOD. In these experiments, oxidation rate of quercetin was faster than those of its glycosides. The results obtained suggest that flavonols can function as antioxidants in chloroplasts by scavenging both O₂-and the radicals formed during lipid peroxidation.     

THE SPECTRAL DISTRIBUTION OF THE LUMINESCENCE EMITTED DURING GROWTH OF THE YEAST SACCHAROMYCES CEREVISIAE AND ITS RELATIONSHIP TO MITOGENETIC RADIATION

Abstract— The spectral distributions of two previously reported weak luminescences from liquid cultures of the yeast Saccharomyces cerevisiae have been determined. During the logarithmic phase of growth, emission was observed as a broad UV band between 200 and 425 nm, and as a visible region band between 525 and 700 nm. During the stationary phase, there were two narrow bands centred at 250 and 650 nm, and a broad band extending from 325 to 525 nm. The UV components are compared with Gurwitsch's mitogenetic radiation, and possible chemical and radiolytic sources of the luminescences are discussed.     

PREVENTION OF UV IRRADIATION INDUCED SUPPRESSION OF MONOCYTE FUNCTIONS BY RETINOIDS AND CAROTENOIDS in vitro

Abstract— The effects of stimulation of human peripheral blood monocytes in vitro with retinoids and carotenoids, and subsequent exposure to ultraviolet light of the B wavelength were measured. The compounds were applied to the monocytes in culture for 24 h, and the washed cells were then exposed to UVB light up to 220 J/m². The compounds tested protected the monocyte from UVB induced damage to phagocytic activity. This protection may be due to the antioxidant or UVB energy-quenching properties of these compounds. Monocyte cytotoxicity against a melanoma cell line was stimulated by exposure to the retinoids or carotenoids, but a protective effect in vitro against UVB damage was not seen for this cell function.     

DOSE-TIME DEPENDENCY OF TUMOR FORMATION BY CHRONIC UV EXPOSURE

-An animal experiment is presented which involved a total of 223 albino hairless mice (Skh hr 1). These mice, excluding 24 of them which served as controls, were divided over 6 groups, each of which received a different but constant daily dose of UV radiation from fluorescent sunlamps (Westinghouse FS40TL12). The range of daily doses encompassed a factor of 33. Data on the response of each group as a whole are presented. The group responses are measured in two ways: (1) the proportion of tumor bearing mice (prevalence), and (2) the average number of tumors per survivor (yield). The data provide information on the variation of the group response with time, daily dose and tumor size.
The relationship between the daily dose and the duration of the treatment till 50% of the mice have tumors is given for several sizes of tumors. From these results, and from direct measurements of tumor growth, it appears that the growth of tumors is virtually dose-independent and, in consequence, only the initiation of tumors is dose-dependent. This implies that the theoretical model of UV-tumorigenesis presented by Blum (1959). based on UV-accelerated growth, is incorrect. It is pointed out that, in similarity to chemo- and radiotumorigenesis, the total dose delivered to a mouse for the induction of tumors has to be higher if a high daily dose is used than if a low daily dose is used. It seems as though an animal becomes more resistant to the UV-stimuius as the rate at which the stimulus is presented is increased: an adaptive phenomenon.     

OCCURRENCE OF PYRIMIDINE-RICH TRACTS IN ASCITES TUMOR DNA AND THE FORMATION OF UV-INDUCED THYMINE DIMERS

Abstract— Analysis of the distribution of pyrimidine-rich tracts (up to decanucleotides) in ascites tumor DNA revealed that these tracts occur predominantly in repetitive sequence of DNA. UV irradiation of ascites DNA resulted in preferential formation of thymine dimers in the pyrimidine-rich tracts as compared to other regions of DNA.     

PROTECTION AGAINST ULTRAVIOLET-B RADIATION-INDUCED LOCAL and SYSTEMIC SUPPRESSION OF CONTACT HYPERSENSITIVITY and EDEMA RESPONSES IN C3H/HeN MICE BY GREEN TEA POLYPHENOLS

Abstract— Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a poly-phenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280–320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. Topical application of GTP (1–6 mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2 kj/m²) resulted in significant protection against local (25–90%) and systemic suppression (23–95%) of CHS and inflammation in mouse dorsal skin (70–80%). These protective effects were dependent on the dose of GTP employed; increasing the dose (1–6 mg/animal) resulted in an increased protective effect (25–93%). The protective effects were also dependent on the dose of UVB (2–32 kJ/m²). Among the four major epicatechin derivatives present in GTP, (‐)-epigallocatechin-3-gallate, the major constituent in GTP, was found to be the most effective in affording protection against UVB-caused CHS and inflammatory responses. Our study suggests that green tea, specifically polyphenols present therein, may be useful against inflammatory dermatoses and immunosuppression caused by solar radiation.     

THE PHOTODYNAMIC IMMOBILIZATION OF ARTEMIA SALINA NAUPLII BY POLYCYCLIC AROMATIC HYDROCARBONS AND ITS RELATIONSHIP TO CARCINOGENIC ACTIVITY

Abstract— The rates of the photosensitized immobilization of the nauplii of the crustacean Artemia salina were measured as a function of irradiation time and the amount of light absorbed by the sensitizers. The nauplii were incubated in the dark in dilute solutions of the sensitizers for periods of 2 and 22 h prior to irradiation. Nineteen carcinogenic and 22 noncarcinogenic polycyclic aromatic hydrocarbons were used as sensitizers. Relative photodynamic activities (RPA) were determined from the rates of immobilization using benz[ c ]acridine as a standard (RPA = 1). High RPA was restricted to carcinogenic compounds with 4 and 5 fused rings, compounds with 6 or more fused rings had low RPA regardless of their carcinogenic activities. The correlation of RPA with carcinogenic activity was excellent ( P = 0.006 and 0.009 for the 2 and 22 h dark incubations, respectively). It is suggested that carcinogenesis by polycyclic aromatics may result from sublethal photodynamic effects.     

A GARLIC EXTRACT PROTECTS FROM ULTRAVIOLET B (280–320 nm) RADIATION-INDUCED SUPPRESSION OF CONTACT HYPERSENSITIVITY

Abstract Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semipurified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis -urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 μg per mouse resulting in 22–46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis -urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis -urocanic acid mediation of this form of immunosuppression.     

PROTEIN ENHANCED INACTIVATION OF VIRAL DNA BY UV RADIATION

Abstract Viral DNA was irradiated in the presence of proteins and assayed for loss of biological activity. Several proteins were found to enhance the inactivation of transfecting ability by UV radiation. The sensitization caused by a particular protein depends upon its amino acid composition. Experiments done at low molar ratios of protein to DNA indicate that a protein-induced lesion could be a highly efficient means of inactivation.     

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.     

UV光引发的丙烯酰胺反相乳液聚合

报道了不透明丙烯酰胺反相乳液体系的UV光引发聚合新方法 .使用普通中压汞灯并辅以适当搅拌 ,UV光引发丙烯酰胺 水 煤油 Span80 +OP 10反相乳液聚合可在 2 0min左右完成 ,所得聚合物分子量达千万 ;聚合过程中不存在恒速期 ,扫描电镜未观察到聚合前后乳胶粒径有数量级的变化 ,表明聚合反应以单体液滴成核为主 .此外 ,考察了光引发剂类型及浓度、单体浓度、乳化剂用量、反应温度等对聚合反应的影响 ,结果表明不同光引发剂的引发活性为Irgacure 2 95 9>(ITX +EDAB) >BDK ,引发剂浓度增加 ,反应速度先增加而后降低 ,存在一最大值 ;单体浓度增加 ,反应速度加快 ,聚合物分子量提高 ;乳化剂用量增加 ,反应速度加快而分子量变化不明显 ;聚合表观活化能为 13 34kJ mol.     

THE DOSE-RESPONSE RELATIONSHIP OF TUMORIGENESIS BY ULTRAVIOLET RADIATION OF 254 nm

Abstract— Groups of albino hairless mice, Skh-hrl, were exposed daily to UVC radiation from low pressure Hg arcs (Philips TUV 40W). These lamps emit predominantly radiation of 254 nm. Three groups of animals were used in the experiments, each receiving a different daily dose.
The results were described with the Weibull probability function. As in earlier studies with UVB. the tumor induction time was proportional to a power of the daily dose. The exponent turned out to be as low as -0.2. This implies that the induction time varied only a little with the daily dose. The average number of tumors per animal was proportional to a power of time. A sample of 73 tumors of at least 4 mm in diameter were investigated histologically. The large majority were classified as squamous cell carcinomas.
A comparison was made with the results of an earlier reported experiment with Westinghouse FS40 sunlamps. Throughout the whole range of daily doses used in the present experiment, UVC was less carcinogenic than UVB. An intriguing difference between the two types of radiation was that the tumors induced by UVC appeared much more scattered over the irradiated parts of the animals than the UVB-induced tumors.