Damage at the root of cell renewal--UV sensitivity of human epidermal stem cells

Background

The epidermis harbors adult stem cells that reside in the basal layer and ensure the continuous maintenance of tissue homeostasis. Various studies imply that stem cells generally possess specific defense mechanisms against several forms of exogenous stress factors. As sun exposition is the most prevalent impact on human skin, this feature would be of particular importance in terms of sensitivity to UV-induced DNA damage.

Objective

To investigate whether human epidermal stem cells are susceptible to UV-induced DNA damage and subsequent functional impairment.

Methods

A method to isolate human epidermal stem cells from suction blister epidermis was established and validated. Volunteers were treated with solar-simulated irradiation on test areas of the forearm and stem cells were isolated from suction blister material of this region. DNA damage was analyzed by staining for cyclobutane thymidine dimers. The functional consequences of UV-induced damages were assessed by colony forming efficiency assays and gene expression analyses.

Results

Compared to an unirradiated control, stem cells isolated from areas that were exposed to solar-simulated radiation showed significantly more DNA lesions. Although the number of stem cells was not reduced by this treatment, a functional impairment of stem cells could be shown by reduced colony forming efficiency and altered gene expression of stem cell markers.

Conclusions

Despite their essential role in skin maintenance, epidermal stem cells are sensitive to physiological doses of UV irradiation in vivo.     

Epidemiologic risk factors of basal cell carcinoma development and age at onset in a Southern European population from Greece

Background: Basal cell carcinoma (BCC) is the most common form of skin cancer with increasing incidence rates worldwide. Methods: To assess the association of BCC with epidemiologic risk factors in a Southern European population from Greece, we conducted a hospital‐based case–control study of 199 patients with BCC and 200 controls. Results: In the multivariate analysis, fair skin colour was associated with increased risk of BCC (OR: 4.9, 95% CI: 2.4–10.0). However, darker skin phototypes III/IV (patient’s reported sun sensitivity/tanning ability) showed a higher BCC risk (OR: 3.9, 95% CI: 1.8–8.5). Persons with occupational UV exposure of 5 years or more had a 2.7‐fold increased risk (95% CI:1.4–5.3). There was an increased risk of BCC related to the number of sunburns after the age of 20 years (OR: 3.2, 95% CI: 1.4–7.3) and solar lentigines (OR: 6.8, 95% CI: 3.6–12.8). Subgroup analysis showed that different risk factors are associated with early onset BCC including the presence of dysplastic nevi (OR: 6.4, 95% CI: 1.5–27.2), the number of weeks per year spent at the beach during childhood (OR: 8.9, 95% CI: 3.3–24.1) and the history of sunburns during childhood (OR:5.0, 95% CI: 1.3–19.1). Conclusions: Fair skin colour was significantly associated with BCC risk. The relation of sunburns during adulthood with BCC underlies the importance of sunburn prevention throughout life time. Early onset BCCs seem to have a different pathogenetic background and were associated with dysplastic nevi as well as intermittent sun exposure and sunburns during the early years of life.     

Narrowband ultraviolet B phototherapy for alopecia areata

Although narrowband ultraviolet B (NB UVB) phototherapy is a well-established treatment in many dermatosis, there is little evidence of efficacy of this method for alopecia areata (AA) treatment in the literature. We undertook a retrospective review of the 25 AA patients treated with NB UVB. Intramuscular triamcinolone acetonide injections per month were used as concomitant treatment in some patients who did not have any contraindication. Eight patients (32%) received monthly intramuscular corticosteroid injections. Four (22.2%) and two (20%) patients achieved excellent response in extensive patchy hair loss patients and entire scalp hair loss patients, respectively. Four of six patients who achieved excellent response also received monthly intramuscular corticosteroid injections. When patients receiving systemic corticosteroid injections were compared with patients given only NB UVB with respect to the treatment responses, a statistically significant difference was seen in patients who achieved excellent response. NB UVB is not an effective treatment with only 20% excellent treatment responses in patients with severe AA, most of whom were also treated with systemic corticosteroids.     

紫外线辐射致晶状体上皮细胞凋亡机制的研究进展

许多流行病学调查和实验研究结果已经证实:紫外线辐射与非先天性白内障的发生、发展有密切的关系;研究表明,晶状体上皮细胞凋亡是非先天性白内障形成的共同细胞学基础.近年来,越来越多的研究发现,晶状体上皮细胞凋亡与非先天性白内障的形成密切相关.本文就紫外线辐射诱导晶状体上皮细胞凋亡的分子机理与白内障发生作一综述.     

Region-specific growth effects in the developing rat prostate following fetal exposure to estrogenic ultraviolet filters

BACKGROUND AND OBJECTIVES: Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. METHODS: Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. RESULTS: Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. CONCLUSIONS: 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals.     

Vitamin D status during pregnancy and aspects of offspring health

Low maternal vitamin D levels during pregnancy have been linked to various health outcomes in the offspring, ranging from periconceptional effects to diseases of adult onset. Maternal and infant cord 25(OH)D levels are highly correlated. Here, we review the available evidence for these adverse health effects. Most of the evidence has arisen from observational epidemiological studies, but randomized controlled trials are now underway. The evidence to date supports that women should be monitored and treated for vitamin D deficiency during pregnancy but optimal and upper limit serum 25(OH)D levels during pregnancy are not known.     

Sunlight,hormone replacement status and colorectal cancer risk in postmenopausal women

A reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross‐sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radiologic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest tertile = 0.40; 95% CI 017, 0.93; p for trend = 0.04. Non‐significant lower risks were also associated with higher levels of outdoor time (≥3.5 hr/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.     

Lens autofluorescence is not increased at high altitude

Purpose: To study the relation between ambient environmental ultraviolet radiation exposure and lens fluorescence. Methods: Non‐invasive lens fluorometry measurements were compared in healthy Bolivian and Danish subjects. Background ultraviolet radiation was 4.5 times higher in Bolivia than in Denmark. Results: No significant differences in lens fluorescence or transmittance were found between Bolivian and Danish volunteers. Conclusion: Age‐corrected lens fluorescence and transmittance were comparable for healthy participants living at high altitude near the equator and healthy volunteers living at sea level at 55° northern latitude. These results suggest that lens ageing, as assessed by lens autofluorometry, is independent of exposure to ultraviolet radiation.