维生素E的防癌抗癌作用

六十年代以前维生素E(VE)一直作为妇科药物应用,六十年代中期后,发现VE是一种“多功能”药物,被临床用来治疗许多疾病。本文旨在阐述VE在防癌抗癌方面的进展。 一、维生素E对正常组织的保护作用 大量研究表明,人类约 90％的癌症与饮食、环境和生活习惯有关,其中约30％～40％的男性及60％的     

酒精对大鼠睾丸的亚慢性氧化损伤及维生素A的保护作用

背景与目的:观察亚慢性摄入酒精对大鼠睾丸结构和功能的损害及维生素A(VitaminA,VA)的保护作用。材料与方法:30只健康雄性成年SD大鼠随机分为对照组、酒精组、酒精 VA组,各组每日分别灌胃给予酒精0、7.5g/kg、酒精7.5g/kg VA50μg/kg,连续13周后对各组大鼠的精子计数、精子活动率、精子畸形率、血清睾酮(Serumtestosterone,T)进行检测,光、电镜观察睾丸生精上皮的组织学改变。同时测定睾丸线粒体中丙二醛(MalonaldehydeMDA)的产生量。结果:与对照组相比,酒精组大鼠精子计数减少,精子活动率下降,精子畸形率升高,血清T水平明显降低,睾丸生精上皮结构破坏,支持细胞和各级生精细胞均有退化变性,睾丸线粒体丙二醛含量明显升高;酒精 VA组较单纯酒精组精子计数、精子活动率有所上升,生精细胞退化变性程度减轻,睾丸线粒体MDA减少,但血清T仍低于对照组。结论:亚慢性摄入酒精抑制精子生成和睾酮合成,补充VA可以限制酒精引起的睾丸过氧化损伤,保护睾丸的生精功能,但是仍有间质细胞合成睾酮障碍。     

维生素E与硫辛酸对光气损伤的抗氧化作用探讨

背景与目的:观察维生素E或/和硫辛酸对光气损伤小鼠的抗氧化作用,为临床救治光气中毒提供实验资料.材料与方法:确定小鼠在光气中毒后体内发生了一定程度的氧化损伤,然后分组给予维生素E或/和硫辛酸,应用全自动血球分析仪进行血液学分析,采用荧光法测定动物肝脏与肺脏MDA.结果:维生素E(6 mg/kg)或/和硫辛酸(0.8 mg/kg)对光气引起的全血WBC、PLT降低有促进恢复作用,对肝脏与肺脏MDA的升高有一定的抑制作用,维生素E单用组效果显著,维生素E与硫辛酸复合组效果最差.结论:维生素E对光气导致的脂质过氧化的抗氧化作用优于硫辛酸,维生素E与硫辛酸复合组效果不及单用.     

维生素C和维生素E对镉诱发精子畸形影响的实验研究

采用小鼠精子畸形实验，证实了给氯化镉０．６ｍｇ／ｋｇ．ｉｐＱｄＸ５。能诱发小鼠精子畸形，并且亦证实了在给氯化镉前五天分别给与维生素Ｃ１ｇ／ｋｇ．ｉｇ．Ｑｄ×１０或维生素Ｅ０５ｇ／ｋｇ．ｉｇＱｄ×１０，均能够对抗氯化镉致精子畸形的作用     

维生素E拮抗氯化汞致小鼠微核作用的研究

本文采用微核试验方法对维生素Ｅ（ＶｉｔＥ）拮抗氯化汞（ＨｇＣｌ２）致小鼠胸骨骨髓多染红细胞微核作用进行了研究，其主要结果有：（１）给小鼠ＶｉｔＥ５ｍｇ／ｋｇ体重及以上剂量时，可显著地降低ＨｇＣｌ２１．０ｍｇ／ｋｇ体重的致小鼠微核作用（Ｐ〈０．００１）；（２）在ＨｇＣｌ２（１．０ｍｇ／ｋｇ）给小鼠染毒前４ｈ和染毒后２ｈ内补充ＶｉｔＥ２０ｍｇ／ｋｇ体重时，均显示明显地拮抗微核作用（Ｐ〈０．００１～Ｐ〉     

维生素E对色拉油烟冷凝物致小鼠毒性作用的影响

本文采用微核试验和精子畸形分析方法,观察维生素Ｅ对色拉油烟冷凝物致小鼠微核率和精子畸形率作用的影响,并作Ｐｏｉｓｓｏｎ 分布资料的Ｕ 检验。结果显示色拉油烟冷凝物５ｍｌ／ｋｇ 和１０ｍｌ／ｋｇ 体重给小鼠灌胃染毒后,其微核率和精子畸形率均明显地高于２－５ｍｌ／ｋｇ 组和单纯色拉油对照组（Ｐ＜ ０．０１） ,而２ ．５ｍｌ／ｋｇ 组未显示致小鼠微核率和精子畸形率升高作用（Ｐ＞ ０．０５） ;给小鼠补充维生素Ｅ２０ｍｇ／ｋｇ 体重后,可显著地降低色拉油烟冷凝物致微核率和精子畸形率升高的作用（Ｐ＜ ０．０１）。故认为色拉油烟冷凝物对小鼠具有明显地毒性作用,而补充维生素Ｅ则可降低其作用。     

维生素E和β-胡萝卜素对小鼠辐射损伤的联合作用

目的：观察维生素E和/或β-胡萝卜素对小鼠经^60Coγ射线辐射后的抗氧化损伤作用,为维生素应用于抗辐射损伤提供实验资料。方法：昆明种小鼠随机分为阴性对照组、辐照组（阳性对照组）、维生素E组（VE组）、β-胡萝卜素组（β-car组）以及维生素E＋β-胡萝卜素组（VE＋β-car组）,共5组。实验小鼠除阴性对照组外,其余各组均一次性给予4.5Gy的^60Coγ射线照射,照射后各组灌胃给受试物,V_E的剂量为30mg/（kg·d）、β-胡萝卜素剂量为20mg/（kg·d）,溶剂为经乙醇及高温处理过的市售菜籽油,对照组给予等体积的纯溶剂,连续灌胃3 d。其后摘眼球取血,处死小鼠并剖取肝脏。用酶联免疫法（ELISA）测定血清中视黄醇结合蛋白（RBP）水平,荧光法测定血清和肝脏的丙二醛（MDA）及还原型谷胱甘肽（GSH）含量。结果：与阴性对照组比较,辐射组RBP显著降低,血清和肝脏中的MDA水平显著升高、GSH水平显著降低（P均〈0.05）。给予VE和/或β-胡萝卜素使^60Coγ射线辐射引起的RBP下降得以回升,对血清和肝脏MDA的升高和GSH的下降均有一定的抑制作用。而VE单用组较VE与β-胡萝卜素联合组的作用效果更显著（P〈0.05）。结论：VE和β-胡萝卜素对^60Coγ射线辐射导致的脂质过氧化均有一定的抗氧化效果,但两者合用具有一定的拮抗作用。     

维生素A和E抗辐射氧化损伤作用的研究

目的：探讨维生素A（vitamin A,V_A）和维生素E（vitamin E,V_E）抗辐射氧化损伤的相互作用。方法：实验分为V_A、V_E抗辐射氧化损伤实验和V_A、V_E联合应用抗辐射氧化损伤实验。前者设阴性对照组、阳性对照组、V_A（30mg/kg）组、V_E（30mg/kg）组及V_A＋V_E半量（均为15mg/kg）联合用药组。各组大鼠每天用受试物灌胃1次,连续灌胃6d,第7天除阴性对照组外其它各组大鼠均以6Gy的~（60）Co照射,再继续灌胃3d后处死大鼠,取血、脑和肝组织,测定MDA、SOD、CAT等指标。V_A、V_E联合应用抗辐射氧化损伤实验设阴性对照组、阳性对照组、V_E组（30mg/kg）、V_E（30mg/kg）与4个不同V_A剂量（分别为2.5、5、10、20mg/kg）的联合应用组,共7组。各组大鼠的处理同前述。结果：与阳性对照相比,单独补充V_A、V_E均可以对辐射损伤产生一定的保护作用,血清、脑、肝脏的MDA含量均显著降低（P均〈0.05）,各种抗氧化酶活性均显著升高（P均〈0.05）。与阴性对照组比较,固定V_E剂量（30mg/kg）与不同V_A剂量联合应用时,大鼠血清、脑、肝脏的MDA含量均显著增加,CAT和SOD活性降低,脑、肝脏组织中V_E含量显著减少（P均〈0.05）,并具有一定的剂量-效应关系。V_A、V_E联合应用时产生的抗氧化作用明显弱于V_A、V_E单独使用的效果。结论：维生素A和维生素E均具有抗辐射氧化损伤的作用,但在一定的剂量下,V_A、V_E联合应用可以产生拮抗作用。     

Bid在维生素E琥珀酸酯诱导SGC-7901细胞凋亡中的作用

背景与目的:研究Bid在维生素E琥珀酸酯(vitamin E succinate,VES)诱导人胃癌SGC-7901细胞凋亡中的作用.材料与方法:在VES诱导SGC-7901细胞凋亡过程中,检测Bid蛋白的活化;用RNA瞬时干扰阻断Bid的表达,再用VES作用SGC-790细胞后,比较Bid阴性表达和Bid阳性表达细胞的凋亡率、线粒体膜电位(△Ψm)、胞浆中细胞色素C含量和PARP活化程度. 结果:VES作用细胞后Bid发生活化;Bid阴性表达细胞的凋亡率较Bid阳性表达细胞降低,线粒体膜电位升高,胞浆中细胞色素C含量减少,PARP活化减弱.结论:在VES诱导SGC-7901细胞凋亡过程中,Bid可能发挥重要作用.     

Polymerase chain reaction–single-strand conformation polymorphism analysis for the VHL gene in chemically induced kidney tumors of rats using intron-derived primers

Von Hippel-Lindau (VHL) gene mutations occur throughout three exons including the exon-intron boundaries in human VHL disease–associated and sporadic renal cell carcinomas. To explore the possible role of the VHL gene in chemically induced rat kidney tumors originating from various cell types, more than 150 bp of Fischer 344 and Noble rat VHL intron sequences flanking the three exons was determined by dideoxy sequencing. Five primer sets were selected for polymerase chain reaction amplification of the coding regions of rat VHL exons 1–3 and the exon-intron boundaries. Tissues from 10 renal eosinophilic epithelial tumors induced by N-nitrosoethyl(2-hydroxyethyl)amine, 10 nephroblastomas induced by N-nitroso-N-ethylurea, and seven renal mesenchymal tumors induced by N-nitrosomethyl(methoxymethyl)amine were examined for VHL mutations by polymerase chain reaction–single-strand conformation polymorphism analysis. No mutation was detected in any tumor type, indicating that VHL mutations are not involved in the pathogenesis of rat kidney tumors arising from the distal region of the renal tubules, the metanephric blastema, or stromal tissues of the cortex. Mol. Carcinog. 19:230–235, 1997. © 1997 Wiley-Liss, Inc. This article is a US Government work and, as such, is the public domain in the United States of America.     

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.     

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland)

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n=34) and with breast cancer (n=32). In postmenopausal women, lower dietary intake (P=0.006) and a smaller concentration of vitamin E in breast adipose tissue (P=0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r=0.25, P=0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.Drs Zhu and Uusitupa are with the Department of Clinical Nutrition, University of Kuopio, Finland, Dr Parviainen is with the Laboratory of Helsinki University, Central Hospital, Helsinki, Finland. Drs Männistö and Pietinen are with the Department of Nutrition, National Public Health Institute, Helsinki, Finland Dr Eskelinen is with the Department of Surgery, and Dr Syrjänen is with the Department of Pathology, University of Kuopio. Address correspondence to Professor Uusitupa, Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. This study was supported by research grants from the Finnish Cancer Society, and by EVO funding for the Breast Cancer Project of Kuopio Cancer Research Center from the Kuopio University Hospital, Finland.     

p16~(INK4A)和HPV16 E7/HPV18 E6在ASCUS中的表达及临床意义

目的:探讨p16 INK4A和HPV16 E7/HPV18 E6在宫颈细胞学诊断为非典型性鳞状细胞不明确意义型(ASCUS)中的表达及筛查潜在宫颈病变的价值。方法:对150例ASCUS患者行阴道镜检查并取活检,同时对该150例患者的TCT标本进行免疫细胞化学染色检测p16INK4A的表达和RT-PCR法检测其中HPV16型E7蛋白和18型E6蛋白(HPV16 E7/HPV18 E6)mRNA的表达。结果:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中表达的阳性率分别为37.33%和46.67%,随着病理级别的增加,p16INK4A和HPV16E7/HPV18 E6 mRNA表达的阳性率也随之增加;p16INK4A和HPV16 E7/HPV18 E6 mRNA筛查ASCUS中宫颈病变的灵敏度、特异度、阳性预测值和阴性预测值分别为0.88、0.95、0.91、0.93和0.81、0.75、0.67、0.86,在p16INK4A和HPV16 E7/HPV18 E6 mRNA阳性的样本中,宫颈病变发生率分别为91.07%和67.14%,均明显高于阴性样本中的发病率7.45%和13.75%(P<0.001);ASCUS中宫颈病变样本中p16INK4A和HPV16 E7/HPV18 E6 mRNA呈高表达,且具有较高的一致性(κ=0.6475)。结论:p16INK4A和HPV16 E7/HPV18 E6 mRNA在ASCUS中病理诊断为宫颈病变的样本中均呈高表达,对筛查潜在的宫颈病变具有重要意义,其中p16INK4A的筛查效能优于HPV16E7/HPV18E6mRNA;p16INK4A能间接反映HPV的转录活性,在ASCUS的分流中有重要意义,且可视性的p16INK4A免疫染色比HPV检测更直观。     

HPV18 E6E7 反义荧光真核表达载体的构建及其在宫颈癌HeLa 细胞中的表达

 目的 构建HPV18型E6E7反义荧光真核表达载体,并观察其对宫颈癌HeLa细胞中HPV18 E6和E7基因表达的影响,探索反义技术用于治疗临床HPV感染及宫颈癌的可能性。方法 以HPV18型全基因质粒为模板,PCR法扩增HPV18型E6E7区716bp片段,利用基因重组技术将目的片段反向插入荧光真核表达载体pEGFP-C1,EcoR I酶切并测序鉴定;采用脂转法将重组质粒pEGFP-HPV18 E6E7as（EGFP-18AS）转染宫颈癌HeLa细胞株,通过RT-PCR及western blot检测细胞中E6、E7 mRNA和蛋白的表达。结果 成功构建HPV18E6E7反义荧光真核表达载体EGFP-18AS,经脂质体转染HeLa细胞,48h后在荧光倒置显微镜下可见明显的绿色荧光,且细胞中E6、E7 mRNA及蛋白表达水平均明显下调。结论 反义荧光真核表达载体可以有效的抑制HPV18E6、E7癌基因的表达,为治疗HPV感染和宫颈癌提供了一种新的方法。     

Development of spontaneous hyperplastic skin lesions and chemically induced skin papillomas in transgenic mice expressing human papillomavirus type 16 E6/E7 genes

Human papillomavirus type 16 (HPV16) has been known to be the major factor for the development of uterine cervical carcinomas. We have developed a line of transgenic mice that express the HPV16 E6 and E7 genes in certain organs using a fusion gene which consists of the tyrosinase promoter and E6/E7 of HPV16, and have chosen the tyrosinase minigene as a co-injected visual marker for the identification of transgenic mice. Our transgenic mice (1) expressed E6/E7 transgene mainly in skin and heart, and (2) showed skin and eye pigmentation profiles, and (3) raised incidence of hyperplastic skin lesions. We had performed two-stage skin carcinogenesis experiment to detect the susceptibility of skin papilloma development in our transgenic mice, using dimethylbenz-anthracene (DMBA) as a initiating agent and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). After 1 week of DMBA treatment (25 μg dissolved in 0.2 ml acetone) and 15 consecutive weeks of TPA treatment (2.5 μg dissolved in 0.2 ml acetone) on the back of transgenic and non-transgenic control mice (Fv-1^b strain mice which are Friend virus B-type susceptible (FVB)/N), papilloma incidence was increased in our transgenic mice 2-fold higher than in control (in female mice, 69.2 vs. 30%, respectively). Thus our transgenic mice may be useful for the development of immunological or other therapies for HPV-associated cancers.