Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.

Background: The action spectrum of solar urticaria varies among cases. In addition, light spectra outside the activating wavelengths can influence the wheal formation in selected patients. Objective: To know the mechanisms of light energy, we examined the effect of wavelengths on the skin and the serum factor. Methods: The patient’s skin and serum were exposed to artificial light sources, in vivo and in vitro, respectively. Results: The action spectrum ranged from UVA to visible light (∼480 nm). The exposure to longer wavelengths immediately after the exposure inhibited the development of urticaria. Conversely, the irradiation of longer wavelengths before exposure increased the wheal formation. Furthermore, UVB irradiation prior to the exposure of urticaria-eliciting light also increased the urticarial reaction, while postirradiation of UVB had no effect. The patient developed an urticarial wheal at the site of injection of her own serum, which had been previously exposed to the action spectrum in vitro. Preirradiation increased the production of the photosensitizer, while postirradiation revealed no effect. Ultrafiltration techniques showed that the molecular weight of the photosensitizer is more than 300 kD. Conclusion: We detected action, inhibition and augmentation spectra in a patient with a severe solar urticaria. Various wavelengths influence the wheal-forming factor in complex interactions.

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The induction of contact hypersensitivity is suppressed when hapten is applied topically to an area irradiated by ultraviolet B (UVB). There is no standardized procedure to induce this local immunosuppression by UVB. We investigated the effects of the following factors on induction of dinitrofluorobenzene contact hypersensitivity in mice. UVB dose, divided UVB exposure, timing of sensitization after irradiation, hapten concentration, hapten volume (application area), sex, age, and simultaneous sensitization on UV-exposed and nonexposed skin. The suppression was enhanced by increasing the UVB dose. When 100 mJ/cm2 of UVB was irradiated, divided daily exposure (25 mJ x 4 d) was more suppressive than single exposure (100 mJ x 1 d). Sensitization 2 d after irradiation (100 mJ/cm2) induced suppression most effectively. When 25 microliters of dinitrofluorobenzene solution was applied to exposed skin, higher concentrations induced lower suppression. When the total dose of hapten was kept constant (92 micrograms), the application of lower concentrations to large areas (0.25%, 25 microliters) caused stronger suppression than higher concentrations (1%, 6.25 microliters) to small areas. Simultaneous sensitization on UV-exposed and nonexposed skin revealed less suppression than sensitization only on exposed skin. The suppression of contact hypersensitivity was significantly greater in young than in old mice. These results provide details that may be useful in designing studies involving immunosuppression by UVB radiation.

Using a panel of monoclonal antibodies directed against keratins (PKK2, CK8.12 and KL1), the effects of ultraviolet B (UVB) and psoralen plus ultraviolet A (PUVA) irradiation on keratin expression in guinea-pig skin were examined immunohistochemically. Following irradiation, whether by UVB or PUVA, rapid alterations in the distribution pattern of keratins were observed in the epidermis. The alterations included the induction of basal cell-type keratins (PKK2 and CK8.12 staining) in the suprabasal layers, with concomitant reduction of the suprabasal-type keratins (KL1 staining). These alterations in keratin expression were observed during the period when DNA synthesis appears to be accelerated by ultraviolet light exposure (5 h-5 days after UVB, and 2-10 days after PUVA irradiation). Therefore, these changes are probably reflections of a proliferative or regenerative state of keratinocytes. This explanation was supported by the result of an experiment involving tape stripping of the epidermal horny layers, which also accelerates DNA synthesis by keratinocytes. Immunohistochemistry appears to be a useful and sensitive method of detecting the effect of ultraviolet light on keratinization.