Interferon-γ links ultraviolet radiation to melanomagenesis in mice

Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients.     

Melanoma genome sequencing reveals frequent PREX2 mutations

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.     

Effects of solar ultraviolet radiation on the photochemical efficiency, photosynthetic pigments and biomass production of Spirulina platensis

Effects of solar ultraviolet radiation (UVR) on Spirulina platensis were studied by investigating its photochemical efficiency, photosynthetic pigments and biomass production while exposed to full spectrum solar radiation or depleted of UVR for understanding how and to what extent UVR influences its photosynthe tic physiology and production. It was found that UVR brought about an extra inhibition of photochemical efficiency by 26%—30%. The greatest inhibition of pho tochemical efficiency in S. platensis was observed at noontime, and then recovered to some extent in late afternoon no matter which treatment they were exposed to. The contents of chlorophyll a, phycocyanin and carotenoids increased during initial stage of the exposure, but decreased with elongated exposure. UVR decre ased the biomass yield by about 6%. It indicated that filtering out UVR of solar radiation would raise the productivity of S. platensis, which is an important factor that should be considered in the production.     

Melanocyte biology and skin pigmentation

Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases.     

青藏高原太阳紫外线辐射及其生物学效应研究现状

青藏高原是世界上紫外辐射最强烈的地区之一,受臭氧层减薄及夏季臭氧低谷效应的影响,使得该地区紫外辐射更加强烈,这引起了人们对该地区紫外辐射研究的关注。紫外辐射具有强烈的生物学效应,能够对人体、动物、植物、微生物造成普遍的影响甚至伤害。青藏高原强烈的紫外辐射为研究紫外辐射的生物学效应提供了天然实验场地及材料,为寻求生物抗紫外辐射的遗传响应、相关生理生化机制提供了可能。通过对这一地区生物群落和生态系统开展紫外辐射相关研究,有可能在强紫外辐射生态学研究上取得突破性进展。     

兰州城区太阳紫外辐射及其与空气污染的关系

利用太阳辐射观测及环境空气质量监测资料，分析了各种天气状况下兰州城区太阳总辐射、紫外辐射的变化特征及其与空气污染的关系．结果表明：自1960-1998年地面接收的太阳辐射总体呈下降趋势，平均下降约12％．晴天紫外辐射占总辐射的4％-5％，紫外辐射的变化趋势与总辐射相同：兰州城区NOx，TSP质量浓度总体上呈下降趋势，O3质量浓度从1985-1989年有所下降，之后又呈上升趋势；紫外辐射与总辐射的比值与大气浑浊度因子S／D相关性较好，二者满足指数关系，相关系数蜘-0.79．兰州城区机动车NOx排放量随汽车保有量的快速增加而呈上升趋势．     

pEgr-Endostatin重组质粒联合电离辐射抗肿瘤效应的实验研究

目的研究pEgr-Endostatin辐射诱导肿瘤的表达特性及其抗肿瘤作用,为提高临床肿瘤放疗疗效提供实验证据.方法 Western blotting法检测pEgr-Endostatin重组质粒联合电离辐射诱导黑色素瘤B16细胞蛋白表达;建立动物模型,用ELISA法检测不同处理组Endostatin的剂量水平,比较不同处理方式的差异.结果 Western blotting法检测结果显示:重组质粒转染的黑色素瘤B16细胞上清中均有Endostatin蛋白表达,而未转染重组质粒的B16细胞和转染空质粒的B16细胞上清中未见Endostatin蛋白表达.ELISA法检测结果表明:体外接受2~10 Gy X射线照射,Endostatin表达水平明显增加,且照射剂量为4 Gy时Endostatin的表达水平最高.2 Gy照射8~72 h后,Endostatin表达水平与假照射组比较明显增加,在48 h时Endostatin表达水平最高.动物实验表明:荷瘤+25 Gy照射组、荷瘤+pEgr-Endostatin照射组、荷瘤+pc DNA3.1+25 Gy照射组和荷瘤+pEgr-Endostatin+25Gy照射组肿瘤生长率显著低于单纯荷瘤组(P0.05#0.01),荷瘤+pEgr-Endostatin+25 Gy照射组亦明显低于荷瘤+25 Gy照射组和荷瘤+pEgr-Endostatin组(P0.05#0.01).结论 pEgr-Endostatin重组质粒联合电离辐射能使Endostatin蛋白表达增加,从而抑制血管内皮细胞生长、发挥抗肿瘤作用.     

紫外老化对沥青性能影响的研究

紫外线辐射是导致沥青老化的主要因素之一.研究了沥青紫外老化前后的物理性能与流变性能,并与热老化前后的物理性能与流变性能进行了对比.低温弯曲梁流变试验(BBR)表明沥青紫外老化后低温抗裂性能减弱.因此,在强烈紫外线作用下导致沥青使用寿命明显缩短,并会产生一系列相关路面病害.     

Flaking and degradation of polyurethane coatings after 2 years of outdoor exposure in Lhasa

The exposure of a high gloss polyurethane aircraft topcoat system with polyurethane intermediate coating and epoxy primer to strong ultraviolet radiation in Lhasa, Tibet was studied by using scanning electron microscopy (SEM), atomic force microscopy (AFM), attenuated total reflectance Fourier-transform infrared (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS). Micro-flakes were found to form on the topcoat surface after exposure and the size and quantity of the flakes increased with the increase of the exposure time. The magnitude of micro-bulges and the topcoat roughness increased after a long exposure to sunlight. Flakes and micro-bulges resulted in the loss of the topcoat gloss. ATR-FTIR and XPS analysis indicated that chain scissions of the polyurea C==O group and the polyurethane C―O―C and CO―NH groups occurred, and the degradation products of NH and carbonyl groups formed due to the exposure. The breaking of the chemical structure of the polyurethane resulted in a decrease in its elasticity and in the adhesion of the flakes to its surface.     

窖泥己酸菌的分离培养与诱变选育

泥窖己酸菌产生的己酸是浓香型大曲酒主体香成分的前体物质之一。从老窖泥中分离纯化出一株产酸能力较高的己酸菌GS5,以其为亲株,通过紫外诱变(照射功率15W,照射距离30cm,时间为3m in),筛选到1株产酸量提高12%的突变株GSUT3,多次继代培养结果表明其产量稳定。研究还发现GSUT3与亲株之间,GSUT3第1代与第8代之间,其生长变化规律和己酸产量的变化规律表现一致。     

应用红细胞光敏模型评价抗光敏中药添加剂

 研究了紫外线或光敏药物单独存在的条件下以及不同照射时间和不同药物浓度条件对模型的影响。建立了长波紫外线诱导光敏药物致使红细胞溶血模型,通过检测红细胞损伤后上清液中的血红蛋白含量,计算溶血率,从而反映细胞损伤程度。结果表明,紫外线低剂量或氯丙嗪单一条件存在时,并不能引起红细胞溶血;当氯丙嗪含量为0.33mg/mL,紫外线照射30min可致红细胞50%溶血,照射60min可使细胞100%溶血。应用此模型对10种中药及植物成分进行检测,筛选出银杏叶提取液、茶多酚和葡萄籽提取液3种具有抗光敏功能的活性成分。其中,银杏叶中主要成分黄酮类物质通过广泛的紫外吸收能力从源头阻止紫外线对细胞膜的损伤,茶多酚、葡萄籽中的多酚类物质通过清除自由基等光产物对细胞膜起到保护作用。     

紫外线辐射坛紫菜离体细胞的初步试验

报道紫外线辐射离体培养的坛紫菜叶状体细胞，对细胞存活率，分裂和发育再生情况进行观察的结果。试验显示，坛紫菜离体细胞对紫外线辐射比较敏感，试验中使用的各种紫外线辐射量对离体细胞都有伤害致死作用，随着辐射量加大，细胞存活率下降，紫外线辐射还具有抑制细胞分裂，诱发与增加再生苗形态变异的作用。根据试验结果，认为紫外线是一种有效的诱变因子，还讨论诱变处理方法及适宜的辐射量。     

Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase

Response to genotoxic stress can be considered as a multistage process involving initiation of cell-cycle arrest and maintenance of arrest during DNA repair. Although maintenance of G2/M checkpoints is known to involve Chk1, Chk2/Rad53 and upstream components, the mechanisms involved in its initiation are less well defined. Here we report that p38 kinase has a critical role in the initiation of a G2 delay after ultraviolet radiation. Inhibition of p38 blocks the rapid initiation of this checkpoint in both human and murine cells after ultraviolet radiation. In vitro, p38 binds and phosphorylates Cdc25B at serines 309 and 361, and Cdc25C at serine 216; phosphorylation of these residues is required for binding to 14-3-3 proteins. In vivo, inhibition of p38 prevents both phosphorylation of Cdc25B at serine 309 and 14-3-3 binding after ultraviolet radiation, and mutation of this site is sufficient to inhibit the checkpoint initiation. In contrast, in vivo Cdc25C binding to 14-3-3 is not affected by p38 inhibition after ultraviolet radiation. We propose that regulation of Cdc25B phosphorylation by p38 is a critical event for initiating the G2/M checkpoint after ultraviolet radiation.     

防紫外线服装防护性能指标及测试方法的比较研究

分析了紫外线对人体的危害及其危害产生的机理，并探讨了紫外线防护的有关基础数据、测试仪器及相关标准．在此基础上，提出紫外线防护及测试等方面进一步研究的工作方向．     

紫外线辐射量变化原因分析

利用菏泽市气象局2003年紫外线辐射强度历史资料数据，统计分析了紫外辐射日变化和年变化规律，总结得出臭氧、太阳高度角、大气透明度和云的变化是影响紫外辐射强度的关键因素．     

紫外线辐射量变化原因分析

利用菏泽市气象局2003年紫外线辐射强度历史资料数据,统计分析了紫外辐射日变化和年变化规律,总结得出臭氧、太阳高度角、大气透明度和云的变化是影响紫外辐射强度的关键因素.     

强紫外线辐射对沥青路用性能的影响

运用薄膜烘箱试验、美国公路战略研究计划(SHRP)的压力老化试验(PAV)和人工强紫外线光照射试验，对沥青路用性能的针入度、延度、软化点和SHRP的动态剪切流变仪(DSR)、弯曲梁流变仪(BBR)指标分析，发现紫外线光老化与热老化对沥青性能的影响在指标上有所不同，从影响沥青路面低温开裂的延度和劲度模量这两项指标来说，紫外线光老化对沥青性能的影响远大于PAV热老化．这对于西部强紫外线辐射地区研究防止沥青路面过早老化和损害有着积极的意义。     

不同入射方式条件下“智能镜面”利用太阳辐射的实验

选取几种典型天气,对几种主要入射方式下“智能镜面”将太阳辐射定向反射进入建筑室内的照度、紫外线辐射强度和眩光情况进行实测及比较.结果表明:采取不同入射方式改善建筑室内的天然采光效果是可行的.入射俯仰角不佳会产生严重的眩光,但采取侧后方入射方式时,眩光得到改善;而采取水平入射时,其反射光的照度及紫外线辐射强度较高.此外,在大气能见度高的天气条件下,太阳辐射的入射率较高、强度较大;而在多云及阴天的天气条件下,紫外线入射率较高,但绝对值较小.     

地球大气对抵达地面太阳紫外辐射量影响的模式研究

在已建立的计算昆明紫外辐射两流模式改进的基础上,进一步计算并讨论了：(1) 各种消光物质的光学厚度变化规律及其对紫外辐射的影响;(2) 季节变化及太阳天顶角变化与紫外辐射的关系;(3) 不同云的光学厚度下紫外辐射的变化;(4) 昆明与北京两地模式计算结果比较,以及与国外相近纬度观测结果进行了比较。     

ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response

Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to gamma-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by gamma-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after gamma-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.