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The influence of topical and systemic vitamin E on ultraviolet light-induced skin damage in hairless mice.

Hairless mice were fed diets containing different levels of vitamin E or received topical applications of the vitamin for three weeks before a single exposure equivalent to one minimal erythematous dose of ultraviolet light provided by an artificial sunlight source. Lipid peroxidation and suppression of incorporation of thymidine into DNA were used to estimate the degree of damage caused by the radiation. Restriction of dietary vitamin E had little effect on degree of epidermal lipid peroxidation or on thymidine incorporation into DNA. High dietary levels of the vitamin did not alter the degree of lipid peroxidation; however, the incorporation of thymidine was restored to levels comparable to those of unirradiated animals. Topical administration of a 1% solution of the vitamin in ethanol 1 or 24 hours before irradiation also restored thymidine incorporation and reduced the degree of lipid peroxidation. The results suggest that both dietary and topical vitamin E are effective in protecting the epidermis against some of the early damage induced by ultraviolet radiation.

Administration, Topical↗

Ultraviolet radiation-induced connective tissue changes in the skin of hairless mice.

Hairless mice (Skh/ hr1 ) were exposed to ultraviolet A (UVA; peak irradiance at 365 nm), or to ultraviolet B (UVB; peak irradiance at 313 nm) radiation. The animals received 12 treatments on alternate days. Connective tissue changes in the skin were monitored by assaying hydroxyproline and desmosine as an indication of collagen and elastin concentrations, respectively. The activities of prolyl hydroxylase and collagen glucosyl-transferase, enzymes participating in the biosynthesis of collagen, were also assayed. The concentration of elastin was significantly increased in mice treated with UVA or UVB. The concentration of collagen was unaffected by the treatments, but the activity of prolyl hydroxylase, reflecting collagen synthetic capacity, was decreased in UVA-treated mice. The collagen glucosyl-transferase activity was unchanged. Irradiation of purified human prolyl hydroxylase with UVA in vitro decreased the enzyme activity at higher doses, but UVB had no effect. The results indicate that definitive changes in the biochemistry of dermal connective tissues can be induced by exposure of mice to UV irradiation.

Animals↗

The effect of various treatments on the size of sebaceous glands of hairless mice and hairless hamsters.

The effect of castration on the size of sebaceous glands of male hairless mice and male hairless hamsters was studied over a period of 4 weeks. Statistically significant decreases in the size of sebaceous glands were observed. The effects of intracutaneous injections of micronized crystalline suspensions of testosterone, testosterone propionate, testosterone phenylpropionate, testosterone decanoate and nandrolone phenylpropionate on the sebaceous glands of castrated hairless mice, castrated hairless hamsters and intact female hairless hamsters were studied over a period of one week. Highly significant increases in sebaceous gland volume were observed 6-7 days after treatment. The effects of subcutaneous and intracutaneous injections of micronized crystalline suspensions of testosterone on the sebaceous glands of intact male and female hairless hamsters were examined at sites local and distal to the injection. Increases in sebaceous gland volume were limited to local sites in the male but increases were observed locally and distally in the female. There was no difference between subcutaneous and intracutaneous injections.

Animals↗

Efficacy of a virion envelope herpes simplex virus vaccine against experimental skin infections in hairless mice.

Hairless mice were immunized with herpes simplex virus type 1 (HSV-1) envelope antigen (EAG), EAG in association with polyriboinosinic . polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose (PICLC), and inactivated purified HSV-1 (VAG). After 2 weeks the mice were challenged by a percutaneous HSV-1 infection in the orofacial (OF) or lumbosacral (LS) skin area. Following immunization a consistent cell-mediated immune response was observed in all immunized mice, although the humoral immune response was very low, or not detectable. After challenge, a marked secondary humoral and cell-mediated immune response developed in all immunized mice, and the animals were protected against the development of skin lesions and the fatal outcome of infection. However, the establishment of latent infections in the sensory ganglia was not prevented by the immunization procedure.

Animals↗

PUVA suppresses the proliferative stimulus produced by stripping on hairless mice.

Hairless mice were fed with 8-methoxypsoralen by gastric tube and exposed to UVA light to produce threshold phototoxic reactions. 3H-thymidine autoradiography revealed no significant difference of the epidermal labelling index as compared to that of nonirradiated animals (4.8 vs 6.2). Single PUVA exposures performed 2,8,14 and 24 hr after tape stripping lead to suppression of a wave of synchronized DNA synthesis present in nonirradiated control animals. These data demonstrate different reactions of stripped and unstripped epidermis to PUVA exposures and offer indirect evidence for the suppression of DNA synthesis in hyperproliferative skin disorders by PUVA in vivo.

Animals↗

Ocular effects of treatment with various psoralen derivatives and ultraviolet-A (UVA) radiation in HRA/Skh hairless mice.

Hairless (HRA/Skh) mice were administered one of four dietary concentrations (50, 100, 625 or 1250 ppm) of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP), or molar equivalent concentrations of 5-methylisopsoralen (5-MIP) or 3-carbethoxypsoralen (3-CPS) by 'pulse feeding' technique, 3 days per week for 13 weeks. For the final 11 weeks psoralen derivative administration was followed by exposure to 0.2 or 48 J/cm2 of unfiltered ultraviolet-A (UVA) radiant energy from FR74T12PUVA lamps. At 0 and 13 weeks eyes were dilated with 0.2% atropine solution and were examined using a binocular indirect ophthalmoscope with a +20.0 D condensing lens. The lids, cornea, anterior chamber and the lens were evaluated for pathological changes. Ocular damage consisting of dense central corneal opacification was seen at significant levels in animals given 8-MOP or 5-MOP and exposed to UVA. In addition, opacities in the area of the posterior lens were seen in all experimental groups and appeared to be related to drug treatment, independent of light exposure, and therefore appeared not to be related to drug-light interaction. Some corneal and lenticular opacification was seen at non-significant levels in all experimental and control groups.

5-Methoxypsoralen↗

Desensitization to DNFB in hairless mice.

Naive hairless mice may be rendered partly tolerant to dinitrofluorobenzene (DNFB) by painting DNFB on skin irradiated with 30 mJ.cm-2 ultraviolet B light (UVB) over 4 days. However, DNFB-sensitized hairless mice show no decrease in sensitivity when repainted with DNFB on skin irradiated with the same dose of UVB. Hence, established hypersensitivity appears not to be reduced by this method of inducing tolerance in naive mice.

Animals↗

Prevention of changes after UV-irradiation by sunscreen products in skin of hairless mice.

Female hairless mice (strain mutant hr/hr) have been irradiated with increasing doses of UV-B over a period of 4 weeks. They were compared with untreated controls Additional groups of 30 mice were treated with milk base or cream base or milk SPF6 or cream SPF6 or cream SPF8 daily before irradiation. No changes of body weight indicating systemic effects were found. Skin thickness was increased significantly after irradiation. These changes were partially antagonized by cream or milk bases and completely prevented by the corresponding formulations containing sunscreen agents. Under the chosen conditions ultimate load of excised skin samples was increased by irradiation. This effect was not reversed by the bases but by the sunscreen products. Ultimate strain of excised skin samples proved to be the most sensitive indicator. The decrease of ultimate strain after irradiation was partially antagonized by the bases. The sunscreen products had more powerful effect. Due to the effects on skin thickness and ultimate load tensile strength and modulus of elasticity did not show significant changes under the chosen conditions. Likewise, collagen and elastin content per gram wet weight did not show significant changes. Considering the increase of thickness of skin which is prevented by sunscreen products one may conclude also a prevention of formation of additional intercellular material. The results prove the value of sunscreen products. Furthermore, they demonstrate a new method for evaluation of chemicals and sun protection preparations.

Animals↗

Liver transglutaminases and vitamin-A deficiency in hairless mice.

In hairless mice, a moderate vitamin-A deficiency, without any clinical signs or weight changes, reduces the activity of soluble cytoplasmic hepatic transglutaminase without affecting the membrane form of the enzyme. This attack of soluble transglutaminase appears to be a biological marker of early deficiency. The relations between this disturbance and the hepatocyte sensitivity to aggressors at this stage are discussed.

Animals↗

Dietary beta-carotene and 13-cis-retinoic acid are not effective in preventing some features of UVB-induced dermal damage in hairless mice.

Albino hairless mice were fed diets containing 10 g/kg feed of beta-carotene and 200 mg/kg feed of 13-cis retinoic acid to assess the ability of these molecules to prevent UVB-induced dermal damage. Diets were administered for 12 weeks prior to UVB exposure and were continued throughout the 20 week irradiation period. The UVB source was a bank of FS-20 sunlamps (280-400 nm: peak 313 nm). Exposures were thrice weekly at 0.1 J/cm2 per exposure for the first 10 weeks and 0.2 J/cm2 per exposure for the second 10 weeks. Histologic evaluation of skin biopsies revealed no difference, between animals fed active or placebo diets, in UVB-induced elastosis, collagen changes or amounts of glycosaminoglycans and proteoglycans of the ground substance.

Animals↗

Selenium inhibits UV-light-induced skin carcinogenesis in hairless mice.

Female hairless inbred hr/hr mice were exposed to UV-B irradiation from Philips TL 40W/12 fluorescent tubes. Fractionated irradiation, given as single daily doses 5 days a week, was gradually increased from 0.04 to 0.4 J/cm2 over 2 weeks. Irradiation at 0.4 J/cm2 was continued for 20 weeks. Selenium supplementation given as sodium selenite in the drinking water at 2, 4 and 8 mg/l began 3 weeks before UV-irradiation and continued thereafter. Development of skin tumors was followed by weekly examinations. Statistical analyses revealed significant dose-dependent selenium-mediated protection against UV-light-induced skin cancer. Leukemia developed in 5 of 150 UV-irradiated mice as opposed to none in a group of 60 unirradiated mice.

Animals↗

Involvement of skin barrier dysfunction in itch-related scratching in special diet-fed hairless mice.

HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. Thus, the prolonged scratching could be itch-related response independent of histamine and serotonin. The application of petrolatum ointment on the skin temporarily alleviated the increase of transepidermal water loss for 60 min after treatment. Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.

Animals↗

Identification of free and esterified hydroxyoctadecadienoates (HODEs) and linoleate-hydroxylating pathway in the epidermis of hairless mice.

Epidermal homogenates of hairless mice contained a large amount of lipid material showing a single peak on reverse phase (RP)-high pressure liquid chromatography (HPLC) with a maximum absorbance of 234 nm, which was different in retention time from arachidonate metabolites such as 12-HETE, 15-HETE and 5-HETE. The production of this material was dependent on exogenous linoleate concentration, protein concentration and buffer pH. This material was identified to be a mixture of 13-HODE and 9-HODE on the basis of UV absorbance spectra, retention times on RP-HPLC, straight phase (SP)-HPLC, gas chromatography-mass spectrometry (GC/MS) and mass spectra obtained. As assessed by SP-HPLC after saponification, these two HODEs were found to exist primarily in esterified forms in the skin. Neither substance was produced following heat denaturation of the homogenate. These results indicate that 13- and 9-HODEs are produced from linoleate enzymatically at physiologically relevant levels in the epidermis of hairless mice. Thus, it is possible that these two materials may play some important role in pathophysiology of the skin.

Animals↗

The sensitivity of the skin of hairless mice to chemical carcinogenesis.

The sensitivity of hairless mice to cutaneous chemical carcinogenesis has been compared with that of normal mice of the same strain with hair. A single application of 125 mug methylcholanthrene in benzene was given to 48 hairless male mice (hr/hr Oslo strain) and to 96 male mice of the same strain with hair. Among hairless mice there were 94% papilloma-bearing animals with a total of 5.9 tumors per animal after 18 months of observation, compared to 22% papilloma-bearing animals with an average of 0.3 tumors per animal among the mice with hair. The hairless mice included 31% carcinoma-bearing and 23% sarcoma-bearing animals, whereas only 1% of the mice with hair were carcinoma bearing and 3% were sarcoma bearing. Hairless mice of the hr/hr Oslo strain are thus not refractory to chemical carcinogenesis, but under the experimental conditions used in this study they are significantly more sensitive than are mice from the same strain with hair. Giovanella et al. reported almost opposite results in 1970 and came to the general conclusion that hairless mice are refractory to chemical carcinogenesis due to lack of hair follicles. Since hairless mice always have some hair follicles and rudimentary pilosebaceous appendages, comparisons between chemical carcinogenesis in hairless mice and mice with hair can neither strengthen nor weaken any theory about the hair follicle origin of epidermoid carcinomas of mouse skin.

Animals↗

Inhibition of methylcholanthrene-induced skin carcinogenesis in hairless mice by dimethyl sulfoxide.

Hairless mice were given 5 topical applications of 470 nmol 20-methylcholanthrene (MCA) at one week intervals. In one experimental group the MCA was dissolved in reagent grade acetone alone, in another group it was dissolved in a mixture consisting of 50% acetone and 50% dimethyl sulfoxide (DMSO). A control group received the mixed solvent alone. The animals were observed for development of papillomas and malignant tumors during 75 weeks. The group treated with MCA in acetone/DMSO had a higher mortality than the two other groups. The admixture of 50% DMSO to the solvent had a significant inhibitory effect on tumor and cancer rates and on cancer yield, whereas no effect could be observed on the tumor yield. Hence, 50% DMSO in the solvent has a moderate, but significant, inhibitor effect on MCA-induced skin carcinogenesis. Similar inhibitory effect of DMSO on the promotion phase in two stage-carcinogenesis protocols have been reported in the literature. The biochemical mechanisms behind this effect are unknown.

Animals↗

Chronic ultraviolet B radiation-induced biochemical changes in the skin of hairless mice.

Skh:HR-1 hairless mice were irradiated chronically with sub-erythemal doses of UVB radiation, and a number of biochemical parameters in the skin were determined after 6, 12, 18, and 24 wk of exposure. The parameters measured were water, collagen, elastin, and glycosaminoglycan content; collagenase and elastase levels; and Bz-Tyr-OEt (N-benzoyl-L-tyrosine ethyl ester) and BAPNA (alpha-N-benzoyl-DL-arginine-p-nitroanilide) hydrolyzing activities. Data for UVB radiation-exposed and chronological age-matched control mice were compared with respect to unit area and to unit mass of skin. On a unit area of skin basis, UVB radiation exposure increased the level of most parameters. The particular exceptions were collagen and collagenase which remained constant. On a mass of skin basis, though, there is an apparent decrease in collagen content because of the increase in the other skin components. This suggests that there is insufficient collagen in UVB radiation-exposed skin to support the increasing mass of the tissue.

Animals↗

The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice.

Groups of hairless mice received one, two, five and fifty applications of 20 nmoles TPA (12-0-tetradecanoylphorbol-13-acetate) on the skin of the back, and were observed for 20 months. The animals developed some papillomas, some squamous cell carcinomas, some fibrosarcomas of the dermis, and some malignant and benign tumours in internal organs. There was a small, not significantly different, incidence of benign and malignant tumours after 1, 2 and 5 paintings, and a significantly higher tumour incidence after 50 applications. Apart from reticuloses, which are commonly seen in these animals, the occurrence of other tumours is believed to be related to the TPA treatment. The results are interpreted as showing that TPA, like croton oil, should be regarded as a complete carcinogen.

Animals↗