不同种类细胞株对UVB紫外线的耐受性初探

目的： 探索几种细胞株对UVB紫外线的耐受性。方法：0、20和50 mJ/cm2紫外线照射后,利用MTT、荧光素酶报告基因检测和克隆形成率实验,检测人表皮细胞HaCaT、人黑色素细胞A875、人肺腺癌细胞A549和H322、人肝癌细胞HepG2的存活及增殖能力。结果：MTT实验结果表明HaCaT、A875、A549、H322和HepG2细胞在受到20和50 mJ/cm2紫外线照射后第1天,细胞活力均显著降低(P<0.05),到照射后第3天,细胞活力仍显著低于未照射组(P<0.05)。克隆形成率实验结果表明,HaCaT、A875和HepG2细胞在照射后,细胞增殖能力受到显著抑制。荧光素酶活性检测实验结果表明,A549细胞在受到20和50 mJ/cm2紫外线照射后第5和第10天,细胞活力显著低于未照射组(P<0.05)。结论：UVB紫外线对表皮细胞、肺腺癌细胞和肝癌细胞的存活和增殖能力均产生影响,其中正常表皮细胞HaCaT细胞对UVB紫外线的耐受性大于肿瘤来源的A875、A549、H322和HepG2细胞。     

HIV病人的紫外线治疗

尽管在80年代早期艾滋病开始流行以来,与HIV-相关的皮肤病在临床和实验室进行了反复的科学性研究,但是皮肤免疫调节机制对免疫系统缺陷时的作用形式仍然不清楚。在紫外线(UV)-照射治疗的过程中UV-照射对皮肤的免疫系统有着重要的作用,并且有效地运用于对蕈样肉芽肿、异位性皮炎、银屑病和一些其他的皮肤病的治疗。然而让人担忧的是紫外线光的免疫抑制作用可能对HIV-阳性病人的主要疾病的负面影响,以致于光治疗作为最后的治疗措施。一些体外的研究和转基因鼠的实验均证实紫外线B(UVB)和PUVA能够诱导病毒在人体内复制。然而迄今为止在人体临床研究中没有证实在UV-治疗下能减短HIV-病人的生存时间。     

软组织扩张术后皮肤组织形态计量学改变

本文对６例额部皮肤软组织扩张术后皮瓣和８例正常人额部皮肤组织进行形态计量学分析及超微结构观察，探讨软组织扩张后“额外”皮肤组织的来源及形态计量学指标的改变。结果表明，扩张后表皮层数、表皮细胞面积及表皮、真皮厚度的检测值均明显高于正常对照组（Ｐ＜０．０１），而且真皮内血管数目增多。提示，软组织扩张后，表皮细胞增殖及真皮内胶原纤维合成增加是“额外”皮肤来源的形态学基础。     

人脐血和外周血单个核细胞增生活性及紫外线B照射抑制作用的研究

目的 :比较人脐血 (CB)和外周血 (PB)单个核细胞 (MCs)的增生活性及其紫外线 B照射 (UVB)在增生活性上的抑制作用。方法 :应用 PHA诱导细胞增生以 3 H- Td R结合检测增生活性 (cpm) ;应用 CBMCs和PBMCs的单向混合淋巴细胞培养 (ML C)测试各自的增生反应 (cpm) ,UVB照射后的 PHA刺激和 ML C抑制作用 ,以未照射细胞的活性百分数表示。结果 :人 CBMCs和 PBMCs cpm平均值无统计学差异 ,但单个实验的标准偏差均显示人 CBMCs的 cpm高于 PBMCs,二者对小剂量 U VB照射均十分敏感 ,CBMCs经 1.0 m J/ cm2～ 2 .0 m J/cm2 U VB照射后 ,PHA刺激和单向 ML C分别下降 5 0 %以下及 2 5 .6 %以下。结论 :CBMCs和 PBMCs不仅有类似反应 ,有可能 CBMCs比 PBMCs有更强的增生反应 ,因此 CB移植需预防 GVHD,U VB照射可明显灭活 CBMCs和PBMCs的增生反应 ,U VB照射可能是更为简便、敏感、安全、有效的体外预防 GVHD的方法 ,可能更适合 CB移植。     

转染抗辐射菌recO基因对紫外线所致皮肤成纤维细胞氧化及炎性损伤的保护作用

背景与目的:观察转染recO基因对紫外线(UVB)诱导的人皮肤成纤维细胞(HSF)抗氧化能力及某些炎性因子分泌的影响.材料与方法:从抗辐射菌(deinococcus radiodurans,Dr)中克隆recO基因连接到pcDNA3.1/NT-GFP-TOPO载体上并转染HSF细胞,recO转染组分别以0、30、90、120 ml/cm2的紫外线(UVB)进行照射,同时设未转染空白组及转染空质粒组2个对照.检测各组受试细胞总超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的变化.结果:UVB照射24 h后,未转染空白组和转染空质粒组总SOD活性水平随UVB照射剂量的增加而下降,MDA、LDH、IL-6及TNF-α含量则随照射剂量的增加而增加,而转染recO组细胞在接受与对照组同等剂量的UVB照射后,SOD分泌增加,IL-6分泌减少,在30～120 mJ/cm2剂量范围内与2个对照组相比差异均具有统计学意义(P均<0.05),而MDA、LDH及TNF-α水平变化不明显(P>0.05).结论:转染recO基因对UVB照射引起的HSF细胞氧化及某些炎性损伤具有一定的保护作用.     

高血压大鼠早期不同脑区小血管超微结构的定量观察

应用ＣＭＩＡＳ医学图像分析仪对８月龄高血压大鼠６个脑区的毛细血管和２个脑区的细动脉进行了定量观察。结果发现：（１）高血压大鼠早期毛细血管的超微结构改变比细动脉更为明显。此期毛细血管的主要病理改变是内皮细胞增生、基底膜增厚以及血管外膜的小灶性坏死，而细动脉则表现为平滑肌细胞增生和基底膜的分层增加；（２）不同脑区毛细血管的病变程度差异较大，深部脑区毛细血管管腔狭窄和管壁增厚的程度明显大于皮层区。本研究为脑血管的定量研究积累了资料，并对上述病理变化的成因以及与临床的关系进行了初步探讨。     

以皮肌炎为首发表现的食管癌1例报告

1　病例介绍患者男性 ,5 3岁。因四肢关节红肿酸痛伴发热 10天 ,于2 0 0 1年 5月 12日入院。患者于入院前 10天无明显诱因出现四肢关节红肿酸痛 ,活动受限 ,局部皮肤温度升高 ,伴畏寒发热 ,就诊于上海某医院 ,拟诊为风湿热 ,淋巴瘤。给予降温激素抗炎等处理后症状有所好转 ,但停药后症状又复发。入院后体检 :体温 38.6℃ ,面部、前胸均见大片红斑丘疹 ,心肺无异常 ,肝脾肋下未触及。四肢各关节肿胀 ,压痛 ,活动受限。胃镜检查结果 :“食管”鳞状细胞癌。背部皮肤活检 :表皮轻度棘层增厚 ,真皮浅层散在炎性细胞 ,表皮真皮交界处和真皮浅层血…     

夏季谨防皮肤癌

炎炎夏日,骄阳似火,仍挡不住外出旅行和度假人们的脚步;软软的沙滩,碧蓝的大海,时尚的日光浴,是人们按捺不住出发冲动的动力……夏日的阳光浴可以改善人体的新陈代谢、增加食欲、改善睡眠、提高机体的抗病能力、晒出时尚的小麦肤色。但如果不讲究科学方法,日晒强度过大,长期接受紫外线的照射,皮肤频繁的暴露在阳光下,反而会导致皮肤癌的发生。那么日常暴晒怎么能引起皮肤癌呢？有足够的证据支持紫外线照射、人体黑色素的防护与免疫系统功能相互作用导致了皮肤癌的发生。在日光中测定人体皮肤,皮肤接受紫外线量最大的部位是头部、面部、颈后、手部,     

选择适合你的防晒霜

因日光或其他光线照射而在皮肤上引起的各种病变或使之加剧的统称为光线性皮肤病,包括通常所指的光毒性皮肤病和光敏性(光变态反应性)皮肤病。出门打伞、戴草帽或穿长袖衣服等“遮盖”方式是最好的避光保护皮肤的方法;其次可以选择合适的防晒护肤霜,使皮肤避免接受过强或过多的紫外线辐射。现在市面上的防晒化妆品具有美白防晒、抗皱防晒、保湿防晒、防水防晒等不同特性,且常标示SPF指数和PA值。所谓SPF指数也就是化妆品防晒指数,是指皮肤抵抗紫外线的时间倍数。它     

急性放射性皮肤溃疡发生发展过程中TGF-β1及其受体TGF-βR1的表达水平:与单纯伤口愈合的定量对比研究

为研究TGF-β1及其受体TGF-βR1在急性放射性皮肤溃疡组织中的表达水平及对溃疡形成、发展、愈合的影响,我们采用雌性Wistar大鼠,以60Coγ射线局部照射法建立急性放射性皮肤溃疡动物模型,并以手术法建立单纯皮肤伤口动物模型,观察病变55天,采用免疫组化、原位杂交和图像分析等方法检测单纯伤口及皮肤溃疡组织中TGF-β1及TGF-βR1的转录和表达水平。研究发现,照后14天照射野内开始出现皮肤溃疡,之后逐渐扩大、融合、加深。皮肤受照射区多种细胞,特别是溃疡床表皮细胞、成纤维细胞及血管内皮细胞中TGF-β1及TGF-βR1的转录和表达水平均较正常皮肤组织明显增强,与单纯伤口组比较,溃疡床的TGF-β1及TGF-βR1阳性细胞数量明显减少,阳性强度减弱不明显。表明放射性皮肤溃疡组织中TGF-β1及TGF-βR1的表达水平降低可能与溃疡发生、发展及难愈合的分子机制相关。     

Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.

Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.     

Inhibitory effect of topical applications of nondenatured soymilk on the formation and growth of UVB-induced skin tumors

Treatment of female SKH-1 hairless mice with ultraviolet B light twice a week for 20 weeks resulted in a population of tumor-free mice with a high risk of developing skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Topical applications of nondenatured soymilk but not heat-denatured soymilk once a day, 5 days a week to these high-risk mice inhibited the formation and growth of skin tumors. Similar topical applications of soybean trypsin inhibitor or Bowman-Birk inhibitor also inhibited the formation and growth of skin tumors, but these agents were less active than nondenatured soymilk. Treatment of miniswine skin with nondenatured soymilk once a day for 5 days prior to UVB irradiation reduced or completely eliminated UVB-induced formation of thymine dimers and apoptotic cells in the epidermis. These data suggest that nondenatured soymilk could be applied to humans to prevent sunlight-induced skin damage and to reduce the risk of skin tumor formation and progression.     

Sunscreens and the prevention of skin aging

It has been well established in both human and animal skin that ultraviolet radiation from both ultraviolet B (UVB) (290 nm-320 nm) and ultraviolet A (UVA) (320 nm-420 nm) can produce profound changes in the skin that with recurrent exposure, cause it to become what we recognize as photoaged skin. Experimental studies in animals have confirmed that some sunscreen chemicals are capable of providing protection against ultraviolet-induced photoaging. It is presumed that regular use of these effective sunscreens will also reduce skin aging changes in humans.     

Accelerated Appearance of Skin Tumors in Hairless Mice by Repeated UV Irradiation with Initial Intense Exposure and Characterization of the Tumors

Skin tumors were produced on the back of hairless mice, HOS (HR/De), by exposure to ultraviolet B light (UVB, 290–320 nm) with 4 different protocols. The first tumors appeared earlier (in 10 weeks in group I and 7 weeks in group III) when initial intense exposure was given, followed by repeated lower-level exposures, than when the mice were exposed to the repeated UV only (in 16 weeks both in group II and group IV). All mice developed skin tumors earlier in the groups given the repeated UV exposures three times a week than in the groups given the exposures twice a week. Most of the skin tumors produced by the UVB exposure were histologically malignant, being transplantable to nude mice, and the cultured cells grown from the tumors were capable of producing tumors when injected into nude mice. The accelerated development of skin tumors by initial intense exposure and short intervals of repeated exposure observed in this study may have implications for humans who expose themselves to intense sunbathing and UV tanning (burning) by fluorescent sun lamps.     

Accelerated appearance of skin tumors in hairless mice by repeated UV irradiation with initial intense exposure and characterization of the tumors.

Skin tumors were produced on the back of hairless mice, HOS (HR/De), by exposure to ultraviolet B light (UVB, 290-320 nm) with 4 different protocols. The first tumors appeared earlier (in 10 weeks in group I and 7 weeks in group III) when initial intense exposure was given, followed by repeated lower-level exposures, than when the mice were exposed to the repeated UV only (in 16 weeks both in group II and group IV). All mice developed skin tumors earlier in the groups given the repeated UV exposures three times a week than in the groups given the exposures twice a week. Most of the skin tumors produced by the UVB exposure were histologically malignant, being transplantable to nude mice, and the cultured cells grown from the tumors were capable of producing tumors when injected into nude mice. The accelerated development of skin tumors by initial intense exposure and short intervals of repeated exposure observed in this study may have implications for humans who expose themselves to intense sunbathing and UV tanning (burning) by fluorescent sun lamps.     

Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of tumor formation in hairless mice

Although ultraviolet B (UVB wavelengths 280-315 nm) dominates the carcinogenic effect of sunlight, ultraviolet A (UVA 315-400 nm) is estimated to contribute 10-20% to the carcinogenic dose; a substantial background that is not affected by a depletion of the ozone layer. Furthermore, certain high-power modern tanning lamps emit mainly long wave UVA (UVA1; 340-400 nm). For a proper risk estimate of UVA exposure its carcinogenicity relative to that of UVB exposure needs to be determined more accurately. To this end we determined the dose-time relationship for skin tumor induction in hairless mice that were irradiated daily with custom-made Philips 365-nm sources. Irradiation of the group exposed to the highest of the four daily doses (430, 240, 140 and 75 kJ/m2) had to be discontinued because severe scratching set in after 3 months (no tumors). In the lower dose-groups the prevalence curves for skin carcinomas (percentage of tumor-bearing mice versus logarithm of time) ran virtually parallel, and were similar to those found with daily UVB exposure. However, the relationship between the daily dose (D) and the median tumor induction time (t50) appeared to differ: with UVB we found that t50 D(r) = constant, with r = 0.6, whereas with UVA1 we found r approximately 0.4. This would imply that 365-nm carcinogenesis shows less of a dose-dependency than UVB carcinogenesis, and that 365-nm radiation becomes more carcinogenic, relative to UVB, as the daily doses are lowered. This relative shift at low doses complicates extrapolation of UVB to UVA risks in humans. Based on the t50 from the lowest dose-group we found that the carcinogenicity at 365 nm (per J/m2) is 0.9 x 10(-4) times that at 293 nm, the wavelength of maximum carcinogenicity in hairless mice. This result for 365-nm carcinogenicity falls well within the margins of error of the wavelength dependency that was estimated earlier from experiments with broadband UV sources.      

Inhibitory effects of orally administered green tea, black tea, and caffeine on skin carcinogenesis in mice previously treated with ultraviolet B light (high-risk mice): relationship to decreased tissue fat.

Treatment of SKH-1 hairless mice with ultraviolet B light (UVB; 30 mJ/cm(2)) twice a week for 22 weeks resulted in tumor-free animals with a high risk of developing malignant and nonmalignant skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Oral administration of green tea or black tea (6 mg tea solids/ml) to UVB-pretreated high-risk SKH-1 mice for 23 weeks after stopping UVB treatment decreased the number of tumors/mouse, decreased the size of the parametrial fat pads, and decreased the thickness of the dermal fat layer away from tumors and directly under tumors. Administration of the decaffeinated teas had little or no effect on these parameters, and adding caffeine (equivalent to the amount in the regular teas) to the decaffeinated teas restored their inhibitory effects. Administration of caffeine alone also decreased the number of tumors/mouse, the size of the parametrial fat pads, and the thickness of the dermal fat layer away from tumors and under tumors. Using data from individual mice and linear regression and correlation analysis, we found a highly significant positive correlation between the thickness of the dermal fat layer away from tumors and the number of tumors/mouse (r = 0.34; P = 0.0001), but the correlation between average tumor size/mouse and the thickness of the dermal fat layer away from tumors was weak (r = 0.16; P = 0.034). The results suggested that p.o. administered tea or caffeine may have decreased tumor multiplicity in part by decreasing fat levels in the dermis. Additional analysis revealed that oral administration of caffeinated beverages (green tea, black tea, decaffeinated green tea plus caffeine, decaffeinated black tea plus caffeine, or caffeine alone) decreased the thickness of the dermal fat layer under large tumors to a much greater extent than under small tumors. This is the first demonstration of a close association between inhibition of carcinogenesis and the lowering of tissue fat levels by a chemopreventive agent.     

Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein

We have previously demonstrated that soybean isoflavone genistein inhibits ultraviolet-B (UVB)-induced skin tumorigenesis in hairless mice. In the present study, we further investigated the possible mechanism(s) of action whereby genistein inhibits photocarcinogenesis with focuses on UVB-induced oxidative events, including hydrogen peroxide (H(2)O(2)) production, lipid peroxidation (as represented by malondialdehyde, MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in vivo. We demonstrated that subacute exposure to UVB substantially increased the level of H(2)O(2), lipid peroxides, and 8-OHdG in skin of hairless mice. In addition, chronic exposure to low-dose UVB (0.9-1.2 kJ/m(2) for 20 weeks) substantially increased the levels of 8-OHdG not only in the epidermis, but also in the internal organs such as liver, brain, and spleen of mice with exception of kidney. However, genistein did not affect the level of UVB-induced pyrimidine dimmers in the same UVB exposed mouse skin, indicating selective inhibition of oxidative DNA damage by genistein. Induction of H(2)O(2) was independent of UVB fluences whereas the levels of MDA and 8-OHdG were induced in an UVB fluence-dependent manner. The results suggest that H(2)O(2) be generated as an acute cutaneous response to UVB irradiation, while MDA and 8-OHdG are accumulated with increasing UVB exposure and more closely related to chronic effects of UVB radiation. Pre-treatment of animals with 10 micromol of genistein 1 h prior to UVB exposure significantly inhibited UVB-induced H(2)O(2) and MDA in skin and 8-OHdG in epidermis as well as internal organs. Suppression of 8-OHdG formation by genistein has been corroborated in purified DNA irradiated with UVA and B. In summary, our results suggest that UVB irradiation elicit a series of oxidative events, which can be substantially inhibited by isoflavonoid genistein through either direct quenching of reactive oxygen species or indirect antiinflammatory effects. Thus, the antioxidative properties of genistein may explain for the mechanisms of anti-photocarcinogenic action of genistein.