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1.
贝叶多孔菌(Polyporusfrondosus,Pf)是属于担子菌亚门多孔菌属的食用菌,其提取液有抑突变作用,本文旨在探讨其作用机理,现将其对大鼠肝脏谷胱甘肽硫转移酶活性、还原住谷胱甘肽水平和细胞色素P450含量影响的研究报道如下:Wistar大鼠24只,雌雄各半,随机分为2组,灌胃分别给予蒸馏水和加热的14.28%Pf水相是取液10ml/kg,每日两次,连续10d,然后剖验,该液对大鼠肝脏GST活性,GSH水平和P450含量均有一定的提高作用,增长率分别为27.50%,47.50%和33.33%。这可能是Pf抑诱变作用的机理之一。  相似文献   

2.
贝叶多孔菌(Polyporus frondosus,Pf)是属于担子菌亚站多孔菌属的食用菌,其提取液有抑突变作用,本文旨在探讨其作用机理,现将其对大鼠肝脏谷胱甘肽硫转移酶活性、还原性谷胱甘肽水平和细胞色素P450含量影响的研究报道如下:Wistar大鼠24只,雌雄各半,随机分为2组,灌胃分别给予蒸馏水和加热的14.28%f水相提取液10ml/kg,每日两次,连续10天,然后剖验,该液对大鼠肝脏GS  相似文献   

3.
国外流行病学和实验动物资料表明,甘蓝、花椰菜等十字花科蔬菜具有肿瘤化学预防作用。作者以种植于杭州郊区的夏光甘蓝(Brassica oleracea Var apitata)菜汁为实验材料,通过微核试验和组织中的细胞色素P450含量、谷胱甘肽-S-转移酶(GST)活性和还原型谷胱甘肽(GSH)含量的测定,在哺乳动物水平,从细胞遗传学和生化毒理学角度探讨该品系甘蓝的抗诱变作用及其机理。  相似文献   

4.
采用一氧化碳差光谱法检测乙双吗啉(AT—1727)和丙双吗啉(AT—2153)等抗肿瘤药物对大鼠肝微粒体细胞色素P_(450)含量的影响。实验发现苯巴比妥对肝微粒体细胞色素P_(450)的诱导作用是对照组的3.6倍,而CCl_4抑制P_(450)的产生,为对照组的40%。AT—1727和AT—2153在50mg/kg大剂量时,对大鼠肝微粒体细胞色素P_(450)含量有轻度诱导作用,但不明显。AT—1727和AT—2153在1.25和25mg/kg时,使大鼠肝微粒体P_(450)含量降低,约为对照组的80—86%。AT—1727在25mg/kg时能抑制苯巴比妥诱导肝微粒体P_(450),AT—2153在25mg/kg时对苯巴比妥诱导肝微粒体P_(450)的作用则无影响。  相似文献   

5.
目的:探讨还原型谷胱甘肽在启动蛋白酶体抑制剂诱导甲状腺癌细胞凋亡中的作用.方法:选取4种人甲状腺未分化癌细胞系ARO、FRO、KTC2和8305C,分别设空白对照组、万珂处理组;流式细胞仪(FCM)检测细胞凋亡;测定还原型谷胱甘肽(GSH)含量、谷氨酸半胱氨酸合成酶(GCL)和谷胱甘肽合成酶(GS)的活性;实时定量PCR法检测GCL和GS mRNA的水平.结果:与对照组相比,蛋白酶体抑制剂万珂对人甲状腺癌细胞系FRO和KTC2具有很强的细胞凋亡诱导作用;万珂处理24 h时,FRO、KTC2细胞中GSH水平下降,差异有统计学意义,P<0.01;ARO和8305C细胞中GSH水平显著增加,差异有统计学意义,P<0.01.万珂处理组FRO和KTC2甲状腺癌细胞中,GCL的活性没有变化而GCL mRNA也仅有轻度增加,P>0.05;但在ARO和8305C细胞中,万珂作用8h后,GCL的活性及mRNA的表达显著增加,差异有统计学意义,P<0.01;而GS活性及mRNA水平在各组细胞中的变化差异均无统计学意义,P>0.05.结论:蛋白酶体抑制剂可诱导耐药的甲状腺癌细胞中GCL转录和活性增高,提高GSH在细胞中的表达,导致蛋白酶体抑制剂诱导的肿瘤细胞凋亡受抑.  相似文献   

6.
诱发大鼠肝癌早期病变中谷胱甘肽S—转移酶的研究   总被引:1,自引:0,他引:1  
林峰  刘毅 《肿瘤》1990,10(5):214-216
谷胱甘肽S-转移酶(GST,E.C.2,5,1,18)是一类分布广泛的多功能蛋白,有多种同工酶形式,在大鼠中至少已发现12种,均为二聚体,分碱性、中性和酸性三大类。肝脏中GST的含量和种类最多,大多为碱性型。GST参与致癌剂的结合和解毒,又发现胎盘型GST(在大鼠中称GST-P或GST7-7,为胎盘中的唯一形式)能在早期肝癌中表达,是一个癌前病变的酶学标志。本文用Solt和Farber制订的顺序诱发大鼠肝癌,研究其早期病变中总GST活力及GST-P含量的变化,并用免疫组织化学方法观察了GST-P在肝组织中的定位。  相似文献   

7.
辛硫磷和灭多威对雌性大鼠生殖系统的联合毒性作用   总被引:4,自引:0,他引:4  
背景与目的: 研究辛硫磷(phoxim,Pho)和灭多威(methomyl,Met)混配对雌性大鼠生殖系统的联合毒性作用。 材料与方法: 选用性成熟健康雌性SD大鼠24只,随机分为辛硫磷组(1/50 LD50 ,29.4 mg/kg Pho)、灭多威组(1/50 LD50 ,0.34 mg/kg Met )、辛硫磷+灭多威组(两者1:1混合)和阴性对照组(蒸馏水), 共4组,每组6只。每天用受试物给大鼠灌胃1次,每周灌胃5 d,连续灌胃 30 d。采用阴道脱落细胞涂片法观察大鼠动情周期的变化;放射免疫法测定血清雌二醇(E2)、孕酮(P4)水平;分光光度法测定其血清和卵巢超氧化物岐化酶(SOD)、谷胱甘肽硫转移酶(GST)的活力以及丙二醛(MDA)、谷胱甘肽(GSH)的含量和血清中丁酰胆碱酯酶(BchE)的含量;并观察子宫及卵巢组织形态的改变。 结果: 析因分析显示,在本试验剂量水平下(0.34 mg/kg) 灭多威使大鼠动情期延长、E2浓度升高、P4含量下降,与对照组比较差异均具有统计学意义 (P<0.01)。辛硫磷组、灭多威组检测结果与阴性对照组比较:血清SOD、GST、GSH 水平升高、MDA含量下降;卵巢SOD、GST、GSH水平下降 、MDA含量升高(P< 0.05或P<0.01)。辛硫磷+灭多威混配组与阴性对照组比较:血清SOD、GST、GSH 水平升高,血清MDA、 P4含量降低;卵巢SOD、GST,GSH 水平降低(P<0.05或 P<0.01),表现为拮抗作用。辛硫磷和灭多威混配组大鼠卵巢的形态未见明显改变,但子宫出现腺体数目增多以及部分腺体扩张的改变。 结论: 在本试验剂量水平下,辛硫磷和灭多威单剂对大鼠生殖系统和机体抗氧化系统产生一定的影响,辛硫磷和灭多威混配可对大鼠生殖系统产生一定的影响。  相似文献   

8.
目的:谷胱甘肽硫转移酶(GST)是一组具有解毒和结合蛋白功能的同工酶,按其等电点的不同分为碱性(α)中性(μ)和酸性(π)3类。近年来有人研究发现,GST在癌前病变及癌组织中有异常表达,与癌的发生、发展以及耐药性的产生密切相关。我们通过刺五加多糖干预小鼠Lewis肺癌侵袭转移过程的研究,探讨谷胱甘肽硫转移酶在小鼠Lewis肺癌中的表达意义。100只雌性C57/BL小鼠(18-22g)随机分为5组:(1)肿瘤组:喂普通饲料,(2)环磷酰胺组:(1mg/g饲料);(3)刺五加组:腹腔注射刺五加注射液0.12ml/只;(4)刺五加+环磷酰胺组:除喂含环磷酰胺饲料外,每天每只小鼠腹腔注0.12ml刺五加注射液;(5)正常对照组:喂普通饲料,实验过程中所有动物均自由进食及饮水。参照Bengt Mannerrik等方法检测瘤、肺组织、GST活性变化。结果显示:(1)刺五加与肿瘤组比较,瘤组织、肺组织、GST活性在各时期虽有变化,但无统计学差异(P>0.05和P<0.01);(3)环磷酰胺组+刺五加组在各时期中GST活性水平明显低于正常对照组、肿瘤组(P<0.05);(4)环磷酰胺与刺五加组比较在各时期中GST性活性水平无统计学差异(P>0.05)。上述结果表明:GST活性水平是一个有应用价值的肺癌标志物,它与肺癌的发生发展有关,可能是肺癌癌变的一个早期标志物,对其进一步研究将有助于肺癌的预防,早期发现早期诊断,可以作为肺癌判断预后的一个参考指标。另外,应用抗癌药物,肝、肾负担加重,可能影响GST的代谢,组织中GST含量降低可能需要一段时间,如检测时间再延长,可能GST含量会有较明显降低。  相似文献   

9.
苯并(a)芘对褐菖肝脏DNA损伤与抗氧活性的影响   总被引:1,自引:0,他引:1  
背景与目的:研究苯并(a)芘BaP对褐菖鲉的毒性效应.材料与方法:将褐菖纳分别暴露于不同浓度(10、100、1 000 ng/L)的苯并(a)芘,0、7、25和50 d以及恢复期7、20 d取鱼肝脏,测定超氧化物歧化酶(SOD)、谷胱甘肽硫转移酶(GST)活性,还原型谷胱甘肽(GSH)含量和DNA单链断裂指标.实验同设溶剂对照组.结果:总SOD活性在Bap暴露7 d后被抑制,25 d后,10 ng/L和100ng/L Bap组SOD活性升高(P<0.05);50 d时,1 000 ng/L组SOD活性显著升高(P<0.05).10 ng/L BaP暴露7 d以及100 ng/L和1 000 ng/L BaP暴露50 d时,GSH含量显著增加(P<0.05).而GST活性在100 ng/L和1 000 ng/L BaP分别暴露25 d、50 d时显著增加,随着暴露时间的延长和暴露浓度的增加,各BaP浓度组DNA损伤呈加重趋势.结论:褐菖鲉肝脏SOD、GST酶活性与GSH含量结合使用以及DNA单链断裂损伤可以作为监测海洋环境中多环芳烃(PAHs)污染的潜在生物标志物.  相似文献   

10.
谷胱甘肽S—转移酶Pi作为肿瘤研究的新系统   总被引:1,自引:0,他引:1  
方福德  左瑾 《中国肿瘤》1995,4(7):25-27
本项目以谷胱甘肽S-转移酶Pi(glutathioneS-transferase,GST-Pi)作为肿瘤研究的新系统,进行了下列各项研究。一、组织、细胞中GST活性及其同工酶组成的研究(一)正常人标本GST具有催化谷航甘肽(GSH)向亲电子化合物及其它类型化合物转移产生结合物的性质,故在试管反应中,给以1mmol/L通网底物CDNB(1-氯-2,4-二硝基苯)和1mmol/LGSH,在适当酶量、温度(25℃)和PBS缓冲液中即可测定活性。GST是一个家族,包含若干种同工酶,根据等电点、底物特异性、免疫交叉反应特性和N-端氨基酸序列资料,可将GST的同工酶…  相似文献   

11.
甘蓝汁的抗诱变作用及其机理研究   总被引:6,自引:0,他引:6  
本文通过微核试验和肝组织中谷胱甘肽-S-转移酶(GST)活性、还原型谷胱甘肽9GSH)含量及细胞色素P450含量测定,在哺乳动物整体水平,从遗传学和生化毒理角学角度研究了甘蓝汁的抗诱变作用及其机理。结果发现,甘蓝汁对环磷酰胺(CP)诱发的小鼠骨髓多染红细胞(PCE)微核细胞率有显著抑制作用,抑制率达47.2%。Wistar大鼠饮甘蓝汁10d后,肝脏GST活性增加25.0%,GSH含量提高47.8%  相似文献   

12.
Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protectagainst xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST)and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate theexcretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, hasdemonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted toinvestigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line tostudy the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established theoptimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene (0-50 μM)on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively.MTT assay of pterostilbene (0-100 μM) showed no cytotoxicity toward the HT-29 cell line. Treatment increasedGST activity in the cell line significantly (p<0.05) at 12.5 and 25.0 μM. In addition, treatment at 50 μM increasedthe GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at 12.5μM and 50 μM. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiyingenzyme levels in HT-29 cells.  相似文献   

13.
Glutathione S-transferases (GST) and glutathione peroxidases (GPO) are important in detoxification. GST activity in the mucosa of the gastrointestinal tract is inversely correlated with the development of gastrointestinal cancer. Helicobacter pylori (H. pylori) infection has been associated with gastric cancer. We studied GST activity and the substrate glutathione (GSH) in patients with H. pylori-associated gastritis. GST activity and isoenzyme levels, GPO activity and GSH levels were studied in antral biopsies of 38 H. /pyfori-positive patients, before and after eradication treatment. In 31 patients in whom H. pylori was successfully eradicated, antral GST enzyme activity before therapy was 532 (465–598) nmol/mg protein-min (mean and 95% confidence interval) and that after therapy was 759 (682–836) nmol/mg protein-min ( P <0.0001). Correspondingly, levels of GST α and GST-P1 were higher after eradication ( P <0.001). GSH concentration significantly increased: 21.2 (16.2–26.2) nmol/mg protein before and 27.1 (23.6–30.6) nmol/mg protein after therapy ( P <0.05). In 7 patients in whom H. pylori was not eradicated, GST activity was 671 (520–823) nmol/mg protein min and 599 (348–850) nmol/mg protein before and after treatment respectively ( P =0.32). GSH levels were 17.4 (9.0–25.7) nmol/mg protein and 18.2 (9.1–27.3) nmol/mg protein, respectively ( P =0.84). No differences in antral GPO enzyme activity, both of selenium (Se)-dependent and total GPO, before and after successful treatment were found. Eradication of H. pylori infection increases GST activity and GSH levels in antral mucosa. Low GST activity and GSH concentration due to H. pylori infection might play a role in gastric carcinogenesis.  相似文献   

14.
章正琰  章正瑛 《癌症》1995,14(6):429-431
本实验将维生素K3作为抗肿瘤药物施用于荷瘤小鼠,检测对肿瘤及宿主肝脏GSH、GSSG含量的影响。结果表明在本实验所用量下,维生素K3对肿瘤宿主肝脏中无论是GSH,还是GSSG都未产生显著性影响,对肿瘤组织中上述两成份的含量可产生剂量依赖性消耗,用药量达80mg/kg时,GSH的消耗量与对照组相比,差异具有显著性。  相似文献   

15.
Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1 administration resulted in clearly reduced DNA damage in liver, to 65% of the level in rats that did not receive grapefruit juice. Furthermore, rats treated with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment also reduced the DNA damage to 74% of the level in rats that did not receive grapefruit juice. No significant differences in the portal blood and liver concentrations of AFB1 were observed between grapefruit juice intake rats and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98, lower numbers of revertant colonies were detected with hepatic microsomes prepared from rats administered grapefruit juice, compared with those from control rats. Microsomal testosterone 6beta-hydroxylation was also lower with rats given grapefruit juice than with control rats. Immunoblot analyses showed a significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content, in microsomes of grapefruit juice-treated rats than in non-treated rats. No significant difference in hepatic glutathione S-transferase (GST) activity and glutathione content was observed in the two groups. GSTA5 protein was not detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal activation system from livers of humans as well as rats. These results suggest that grapefruit juice intake suppresses AFB1-induced liver DNA damage through inactivation of the metabolic activation potency for AFB1 in rat liver.  相似文献   

16.
Patients with Barrett's esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class α, μ, π, and θ isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett's esophagus were taken from both Barrett's and adjacent normal squamous epithelium. GST enzyme activity towards 1–chloro-2,4–dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon's signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35%, and GST μ, GST π and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST α and GST θ levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett's epithelium may therefore contribute to the increased cancer risk in this tissue.  相似文献   

17.
The chemoprotective effect of garden cress (GC, Lepidium sativum) and its constituents, glucotropaeolin (GT) and benzylisothiocyanate (BITC), a breakdown product of GT, towards 2-amino-3-methyl-imidazo [4,5-f] quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions was investigated in single cell gel electrophoresis (SCGE) assays and in aberrant crypt foci (ACF) experiments, respectively. Pretreatment of F344 rats with either fresh GC juice (0.8 ml), GT (150 mg/kg) or BITC (70 mg/kg) for three consecutive days caused a significant (P < 0.05) reduction in IQ (90 mg/kg, 0.2 ml corn oil/animal)-induced DNA damage in colon and liver cells in the range of 75-92%. Chemical analysis of GC juice showed that BITC does not account for the effects of the juice as its concentration in the juice was found to be 1000-fold lower than the dose required to cause a chemoprotective effect. Parallel to the chemoprotection experiments, the modulation of the activities of cytochrome P4501A2, glutathione-S-transferase (GST) and UDP glucuronosyltransferase (UDPGT) by GC juice, GT and BITC was studied. Whereas GT and BITC did not affect the activity of any of the enzymes significantly, GC juice caused a significant (P < 0.05) increase in the activity of hepatic UDPGT-2. In the ACF assay, IQ was administered by gavage on 10 alternating days in corn oil (dose 100 mg/kg). Five days before and during IQ treatment, subgroups received drinking water which contained 5% cress juice. The total number of IQ-induced aberrant crypts and ACF as well as ACF with crypt multiplicity of > or =4 were reduced significantly (P < 0.05) in the group that received IQ plus GC juice compared with the group that was fed with IQ only. However, crypt multiplicity was not significantly different in these two groups when all ACF with all classes of crypt multiplicity were considered in the analysis. This is the first report on the inhibition of HA-induced DNA damage and preneoplastic lesions by a cruciferous plant. Our findings suggest that the chemoprotective effect of GC is mediated through enhancement of detoxification of IQ by UDPGT.  相似文献   

18.
Patients with villous atrophy due to coeliac disease have an increased risk of developing small intestinal malignancies. Intestinal glutathione (GSH) and glutathione S‐transferases (GST) are involved in the protection against carcinogenesis. The aim of this study was to evaluate GSH content and GST enzyme activity in small intestinal mucosa of untreated coeliacs compared to controls. We evaluated GSH content and GST enzyme activity, including the levels of GST classes α, μ, π, θ in small intestinal biopsies of untreated coeliacs (flat mucosa, Marsh IHC, n=12) compared to normal subjects (n=23). Next, we evaluated GSH and GST's in coeliacs in remission (Marsh 0‐1, n=11), coeliacs with persisting villous atrophy while on a gluten‐free diet (partial villous atrophy, Marsh IIIA (n=5); subtotal villous atrophy, Marsh IIIB (n=6) and patients with infiltrative/crypt‐hyperplastic Marsh II lesions (n=4). Total GST enzyme activity and content of GSTa are markedly suppressed in Marsh IIIC lesions compared to controls (resp. 220±79 vs. 4641189 nmol/mg protein‐min (P<0.001) and 2.79±2.46 vs. 6.47±2.29 μg/mg protein (P<0.001). In coeliacs in remission these levels normalized. Total GST enzyme activity and GSTα levels are proportionately lowered according to the degree of mucosal pathology in Marsh II, IIIA and IIIB. (Spearman's σ correlation coefficient for total GST, ‐0.596, P<0.001; GSTα, ‐0.620, P<0.001). GSTμ, π and θ and GSH levels are not significantly different in the selected study groups of mucosal pathology compared to controls. Total GST enzyme activity and content of GSTα in small intestinal mucosa are significantly lower in untreated coeliac disease compared to controls. In Marsh II, IIIA and IIIB, GST enzyme activity and GSTα content are proportionally lower according to the degree of mucosal pathology. Normal values are seen in coeliacs in remission. This correlation between coeliac disease and a suppressed GSH/GST detoxification system may explain in part the carcinogenic risk in untreated coeliac disease.  相似文献   

19.
血液肿瘤细胞对氧化砷的敏感性与其抗氧化能力的关系   总被引:2,自引:0,他引:2  
目的 探讨血液肿瘤细胞对三氧化二砷 (As2 O3 )的敏感性和细胞抗氧化能力的关系。方法 应用 9个血液肿瘤细胞系 ,通过细胞活力、形态学和流式细胞仪检测细胞凋亡 ,并测定细胞系的谷胱甘肽 (GSH)含量和 4种抗氧化酶的活性。结果 除了HL 6 0、U937、K5 6 2和Jurkat细胞外 ,其他5个细胞对As2 O3 诱导的凋亡敏感。与敏感细胞系比较 ,As2 O3 耐受细胞系存在较高的GSH含量和(或 )过氧化氢酶活性。谷胱甘肽过氧化物酶、谷胱甘肽S转移酶和超氧化物歧化酶活性与细胞对As2 O3 诱导凋亡效应敏感性无明显相关。结论 细胞内GSH水平和过氧化氢酶的活性是决定血液肿瘤细胞对As2 O3 敏感性的重要因素。  相似文献   

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