CCT亚基γ基因在AFB_1诱发大鼠肝癌过程中表达的变化

目的探讨AFB1诱发肝癌过程中CCT亚基γ基因蛋白的表达及其意义。方法 45只Wistar大鼠随机分为AFB1组和对照组,AFB1组以200μg/kg体重腹腔注射AFB1,第13周、第33周和第53周对大鼠进行肝活检,第73周处死全部动物并取肝组织。用免疫组化法检测AFB1诱发肝癌过程中不同时期CCT亚基γ基因蛋白的表达情况。结果在第73周AFB1组CCT亚基γ基因蛋白表达水平显著高于对照组(P<0.05)。同一组不同时段比较,随着诱癌的进行,CCT亚基γ基因蛋白表达上调,第73周AFB1组CCT亚基γ基因蛋白的表达水平不仅明显高于第13周,而且亦高于第33周(P<0.01)。其余各组和同组不同时段之间CCT亚基γ基因蛋白的表达差异无统计学意义(P>0.05)。AFB1组中发生肝癌的动物肝组织CCT亚基γ基因蛋白表达率为100%(10/10),显著高于同期对照组CCT亚基γ基因蛋白的表达率30%(3/10)(P<0.05)。结论 AFB1诱癌过程中CCT亚基γ基因蛋白表达上调,CCT亚基γ基因蛋白有可能参与了肝细胞癌的发生和发展。     

基于RNA-seq技术的宫颈癌与癌旁组织差异表达基因分析

目的 探讨宫颈癌的发病机制.方法 应用RNA-seq技术分析3对宫颈癌及癌旁组织转录组,利用生物信息方法对差异基因进行基因本体(GO)分析和通路富集性分析.结果 在宫颈癌组织中发现1755个差异表达基因,其中758个基因表达上调,997个基因表达下调.功能富集分析表明,差异基因富集于细胞粘附、DNA损伤有关的信号通路上.且宫颈癌组织中发现RAB22A-BCAS1等融合基因.结论 细胞粘附信号通路、RAB22A-BCAS1融合基因可能与宫颈癌的发生机制有关.     

CCT亚基γ基因在AFB1诱发大鼠肝癌过程中表达的变化

目的探讨AFB1诱发肝癌过程中CCT亚基γ基因蛋白的表达及其意义。方法45只Wistar大鼠随机分为AFB。组和对照组,AFB1组以200ug／kg体重腹腔注射AFB1,第13周、第33周和第53周对大鼠进行肝活检,第73周处死全部动物并取肝组织。用免疫组化法检测AFB1诱发肝癌过程中不同时期CCT亚基γ基因蛋白的表达情况。结果在第73周AFB1组CCT亚基γ基因蛋白表达水平显著高于对照组（P〈0．05）。同一组不同时段比较,随着诱癌的进行,CCT亚基γ基因蛋白表达上调,第73周AFB1组CCT亚基γ基因蛋白的表达水平不仅明显高于第13周,而且亦高于第33周（P〈0．01）。其余各组和同组不同时段之间CCT亚基γ基因蛋白的表达差异无统计学意义（P〉0．05）。AFB。组中发生肝癌的动物肝组织CCT亚基γ基因蛋白表达率为100％（10／10）,显著高于同期对照组CCT亚基γ基因蛋白的表达率30％（3／10）（P〈0．05）。结论AFB,诱癌过程中CCT亚基γ基因蛋白表达上调,CCT亚基γ基因蛋白有可能参与了肝细胞癌的发生和发展。     

基因可变剪接在癌症发生和治疗中的研究进展

［摘要］ 可变剪接指从单个基因产生多种mRNA同种型，是转录后调控的重要方式之一。可变剪接不仅影响人体正常生长发育过程，而且在包括癌症在内的多种疾病发生发展中扮演重要角色。癌组织的剪接变化通常是全局的而不是基因特异性的，异常的剪接模式控制癌症的主要特征。遗传、表观遗传、剪接因子网络差异表达及选择性转录起始或终止等多种途径巩固了特定促癌或抑癌同种型的优势表达，进而影响癌症进程。此外，近年来研究，证明呈组织或阶段特异性表达的剪接同种型有作为癌症生物标志物及治疗靶标的潜能。本文通过全局剪接变化影响肿瘤进展、可变剪接影响癌症进展的途径及可变剪接提示癌症监控和治疗新策略3 个方面进行综述。     

CYP3A4在黄曲霉毒素B1诱发大鼠肝癌过程中的表达及意义

探讨CYP3A4在黄曲霉毒素B1（AFB1）实验诱发大鼠肝癌过程中的活性变化及其在肝癌发生过程中的意义。方法:雄性、4周龄、Wistar大鼠随机分为AFB1组和对照组;AFB1组腹腔注射AFB1,对照组则给与溶媒二甲基亚砜。在诱发肝癌过程中,分别于第13、23、33、43、53、63周对大鼠进行肝活检;实验至第73周处死全部动物取肝组织;利用大鼠肝组织微粒体混合酶体外代谢体系,采用荧光分光光度定量法动态检测肝标本中CYP3A4酶活性。结果:AFB1组肝细胞癌发生率为58.8%（10/17）;对照组肝细胞癌发生率为0（0/16）,两组间肝癌发生率比较,AFB1组显著高于对照组（P=0.001）。两组大鼠肝组织代谢酶CYP3A4活性都有不同程度的变化。肝组织CYP3A4活性从13 w开始逐渐升高,至23 w达顶峰,然后逐渐降低,到43 w又升高,出现双波峰变化;从13 w至53 w不同时段AFB1组肝组织CYP3A4活性显著低于对照组（P<0.01）。但是至63 w时AFB1组肝组织CYP3A4活性基本接近对照组（P=0.5086）。结论:CYP3A4活性在AFB1诱癌过程中受到抑制,可能是由于癌变早期的细胞减少对致癌物质的活化有关;CYP3A4活性在AFB1诱癌过程中的表达起伏变化,是由于基因多态性较大程度上影响蛋白表达水平的结果。      

银杏叶提取物对AFB1所致大鼠肝癌基因P16Ink4a mRNA及蛋白表达的影响

  目的  动态观察银杏叶提取物(ginkgo biloba extract, EGb761)在抑制黄曲霉毒素B1(AFB1)诱发大鼠肝癌过程中对肝组织相关基因P161nk4a mRNA表达水平的影响, 进一步从分子生物学水平揭示银杏叶提取物抗癌的机制及其效果。  方法  将70只4周龄Wistar雄性大鼠随机分为3组: AFB1组(25只), AFB1+EGb761组(25只)及对照组(20只)。在诱发肝癌过程中, 分别于第13、33及53周对大鼠进行肝组织活检; 至第73周处死全部动物取肝组织。应用实时荧光定量PCR和Westernblot技术动态检测肝组织中P16Ink4a mRNA及相应蛋白的表达情况。  结果  AFB1组原发性肝癌发生率为58.8%(10/17);AFB1+EGb761组为29.4%(5/17);对照组为0(0/16) AFB1+EGb761组肝癌发生率显著低于AFB1组(P < 0.05)。AFB1+EGb761组的肝组织P16Ink4amRNA及相应蛋白表达水平在第53周及第73周时均明显高于AFB1组, 差异有统计学意义(P < 0.05)。  结论  银杏叶提取物(EGb761)具有抑制AFB1致大鼠肝癌的作用。其机制可能与调控肝细胞抑癌基因P16Ink4a mRNA表达水平有关。      

敲低纤维连接蛋白1表达抑制甲状腺乳头状癌细胞增殖北大核心

目的:研究纤维连接蛋白1(fibronectin 1,FN1)对甲状腺乳头状癌细胞增殖的影响及相关分子机制。方法:采用慢病毒感染的方法敲低甲状腺乳头状癌细胞TPC-1和BCPAP中FN1的表达,通过CCK8实验证明FN1对甲状腺乳头状癌增殖的影响;采用三代测序技术对FN1敲低的TPC-1细胞及其对照组进行全长转录组测序,筛选差异表达基因,使用BMKCloud在线分析软件对差异基因行GO功能富集分析和KEGG通路富集分析,通过STRING数据库对筛选出的差异表达基因进行蛋白互作网络分析。结果:敲低FN1能够抑制甲状腺乳头状癌细胞的增殖;FN1敲低后与对照组转录本的表达差异明显,GO功能富集显示差异转录本主要集中在细胞过程、细胞部分的组成、细胞黏附功能、催化活性功能,在KEGG富集上显示在HIF-1信号途径、糖酵解、碳代谢富集明显,PPI结果显示FN1和HSPA8是关键蛋白。结论:本研究通过细胞实验证明敲低FN1的表达能够抑制甲状腺乳头状癌细胞的增殖,测序及生物信息学分析为后续甲状腺乳头状癌诊断及靶向治疗的进一步研究提供数据支持。     

不同因素诱发的树齮肝癌组织的基因表达差异

背景与目的：以往用基因芯片技术筛选肝癌相关基因的研究一般以癌旁组织作为对照与肝癌组织比较,但肝癌的癌旁组织常含有肝炎、肝硬化、增生结节等病变。为了探讨肝癌发生的分子机制及有关的基因改变,本研究用树鼩动物模型对病因不完全相同的两组动物的肝癌和其自身的癌发生前活检肝组织进行基因表达水平的比较。方法：实验树鼩分两组,黄曲霉紊B1(aflatoxin B1,AFBl)组单纯喂AFBl,HBV AFBl组先感染人乙型肝炎病毒(hepatitis B virus,HBV),然后喂AFB1。实验期间定期抽血检查HBV感染标志,并剖腹取肝组织活检。动物出现肝癌后,两组各取2例肝癌组织及其冷冻保存的癌发生前活检肝组织,用cDNA微阵列技术检测、比较各例肝癌组织和其相应癌发生前活检肝组织的基因表达水平,分析不同病因的两组肝癌组织的差异表达基因的异同。结果：肝癌发生率在AFB1组和HBV AFB1组分别为73．3％和77．8％。两组肝癌组织都有较大量的基因发生表达水平的改变,但在AFB1组以上调改变为主,在HBV AFB1组以下调改变为主。在受测的588个(16个功能组)已知与人类肿瘤有关的基因中,两组有相同改变的基因共11个,它们主要分布在3个功能基因组,即凋亡相关蛋白组,DNA合成、修复和重组蛋白组以及生长因子、细胞因子和趋化因子组。结论：HBV对单纯AFB1引起的基因表达改变有一定影响。     

大鼠肝癌组织中DLC1、ASC、p16和DLK1基因甲基化状态与肝癌的关系

目的 探讨大鼠肝癌组织中DLC1、ASC、p16和DLK1基因启动子区甲基化状态与肝癌发生的关系。方法 55只Wistar雄性大鼠随机分为黄曲霉毒素B₁（Aflatoxin B₁,AFB₁）实验组（35只）和空白对照组（20只）,用AFB₁诱发大鼠肝癌并建立大鼠实验动物肝癌模型。用甲基化特异性PCR（MS-PCR）技术和琼脂糖凝胶电泳方法检测大鼠肝癌组织及正常肝脏组织中DLC1、ASC、p16和DLK1基因启动子区的甲基化情况,分析4个基因的甲基化状态与肝癌发生的关系。结果 在实验第52周可见大鼠肝脏发生典型的肝癌病理学改变,实验诱发大鼠肝癌模型制作成功。MS-PCR技术检测显示在大鼠肝癌组织中DLC1、ASC、p16和DLK1基因启动子区的甲基化率分别为83.3%、93.3%、86.7%和10.0%,在大鼠正常肝脏组织中的甲基化率分别为14.3%、35.7%、21.4%和85.7%,二者比较差异均有统计学意义（P均<0.05）。琼脂糖凝胶电泳法检测显示4种基因甲基化均为阳性。结论 大鼠肝癌组织中DLC1、ASC、p16基因启动子区高度甲基化,DLK1基因启动子呈低甲基化水平,提示 DLC1、ASC、p16和DLK1基因启动子区的异常甲基化与大鼠肝癌发生的关系密切。     

感染土拨鼠乙肝病毒的小鼠非瘤组织与肝细胞癌的差异表达基因

目的 确定土拨鼠HBV引发的肝癌组织和非癌组织中差异表达的基因。方法 通过抑制消减杂交法克隆土拨鼠HBV引发的肝癌组织和非癌组织中差异表达的基因；对差异表达基因进行DNA序列测定后于GeneBank内分析共同源性；应用原位杂交确定差异基因在肝癌组织和非癌组织中的特异性表达。结果 通过抑制水服装厂 杂交共得到了14条肿瘤组织差异表达的基因片段，其中，肿瘤组织和非瘤组织共有的8条基因与GeneBank中的已知基因同源，肿瘤组织来源的5条基因和非瘤组织来源的1条基因在GeneBank中未找到同源基因，原位杂交差异基因在肝癌组织和非癌组织中均为特异性表达。结论 通过抑制消减杂交获得了14条肝癌组织和非癌组织差异表达的基因。为理解HBV诱发肝癌的机理提供了一定的理论依据。     

Hsa-miR-4282对肝癌细胞系SMMC-7721生长的影响

目的  探讨Hsa-miR-4282在肝癌细胞系SMMC-7721中的表达及其对细胞生长的影响。方法 采用实时荧光定量PCR法检测Hsa-miR-4282在人正常肝上皮细胞系HL-7702和人肝癌细胞系MHCC97-H、SMMC-7721，以及 20例肝癌组织及其相应癌旁组织中的表达。采用瞬时转染法将Hsa-miR-4282 mimics（上调组）和Hsa-miR-4282 inhibitor（下调组）分别转染肝癌SMMC-7721细胞，上调组和下调组分别设置相应阴性对照组。转染后采用MTT法检测细胞增殖能力，平板克隆形成实验检测细胞克隆形成能力，流式细胞仪检测细胞凋亡能力。结果 Hsa-miR-4282在肝癌组织、肝癌细胞MHCC97-H及肝癌细胞SMMC-7721中的表达均低于癌旁组织及正常肝细胞HL-7702（P＜0.05）。MTT实验结果显示，Hsa-miR-4282上调后肝癌SMMC-7721细胞的OD值低于其阴性对照组，而下调后OD值高于其阴性对照组 （P＜0.05）。平板克隆形成实验显示，下调组的细胞克隆数高于其阴性对照组［（240±7） 个 vs （191±10） 个，P=0.005）］，而上调组细胞克隆数低于基阴性对照组［（146±10） 个 vs （193±12） 个，P=0.013）］。流式细胞仪检测结果显示，Hsa-miR-4282上调组细胞凋亡率较其阴性对照组升高［（23.89±1.89）% vs（16.6±1.14）%，P=0.009）］，下调组细胞凋亡率较期阴性对照组降低［（14.98±0.46）% vs （17.79±0.73）%，P=0.010］。结论 Hsa-miR-4282上调可抑制肝癌SMMC-7721细胞增殖，促进细胞凋亡，可能与肝癌的发病机制有关。     

Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry.

Previous studies have demonstrated that dietary administration of the schistosomicidal drug 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) ameliorates the hepatotoxicity of aflatoxin B1 (AFB1). Notably, mortality, altered hepatic function, hepatic AFB1-DNA adduct levels, and expression of hepatic enzyme-altered foci were markedly reduced in the rat by concurrent feeding of oltipraz during exposures to AFB1. Collectively, these studies prompted us to evaluate the chemoprotective properties of oltipraz against AFB1-induced liver cancer. In addition, preliminary molecular dosimetry studies were undertaken to determine the utility of measurements of urinary aflatoxin-N7-guanine excretion as a marker of relative risk for hepatocarcinogenesis in AFB1-exposed rats. For the carcinogenesis studies, 5-wk-old male F344 rats were randomly divided into two groups. One group (55 rats) received the AIN-76A diet, and the other group (56 rats) received the AIN-76A diet supplemented with 0.075% oltipraz. The oltipraz-supplemented diet was fed for 4 wk. Beginning 1 wk after starting the experimental diets, all rats in both groups received 25 micrograms of AFB1/rat/day by gavage for 5 days per wk over the next 2 wk. One wk following cessation of dosing with AFB1, oltipraz was removed from the diet, and all rats were fed the AIN-76A diet for the remainder of the experiment. At 3 mo after dosing, livers of ten sentinel rats from each group were analyzed for the burden of gamma-glutamyltranspeptidase-positive foci. In accord with previous findings, rats fed the oltipraz-supplemented diet exhibited substantial reductions in the focal burden (97% reduction; P less than 0.05) of these AFB1-induced lesions. The remaining rats were maintained for the cancer study until they became moribund or the termination of the experiment at 23 mo. Gross liver lesions were identified at autopsy and confirmed by microscopic evaluation. An 11% incidence of hepatocellular carcinoma was observed in the AFB1-treated, control diet-fed rats. An additional 9% of this group had hepatocellular adenomas. Oltipraz afforded complete protection against both AFB1-induced hepatocellular neoplasms. Using Kaplan-Meier survival analyses, rats in the oltipraz group had a significantly (P less than 0.02) longer life span and an increased survival free of liver tumors (P less than 0.0002). Molecular dosimetry studies used rats fed either the oltipraz-supplemented or control diet for 1 wk and then challenged with a single dose of AFB1 to examine the initial rates of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 excreted in the urine.(ABSTRACT TRUNCATED AT 400 WORDS)     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

何首乌有效成分对大鼠骨癌痛的镇痛效果

目的  探讨何首乌有效成分对大鼠骨癌痛的镇痛作用。方法 将36只SPF级雌性SD大鼠随机分成3组：A组为正常空白对照（n=6），B组大鼠注射无菌生理盐水（n=6），C组大鼠左后腿胫骨注射乳腺癌细胞walker256建立骨癌痛模型（n=24）。建立骨癌痛模型的C组SD大鼠按灌胃药物随机分成C1、C2、C3、C4 4组，每组6只。建模成功后14 d、15 d、16 d连续对C1~C4组大鼠分别灌胃生理盐水（2 mL）、二苯乙烯苷（60 mg/mL，2 mL）、大黄素（60 mg/mL，2 mL）和儿茶素（60 mg/mL，2 mL）。每次灌胃前、灌胃后30 min、灌胃后1.0 h测量大鼠左脚掌的机械痛阈值。结果 癌痛模型喂养第5天起，与A、B两组比较，C组大鼠机械痛阈值降低（P<0.05），骨质明显破坏；A、B两组大鼠机械痛阈值无明显差异，骨质结构正常。C2组大鼠各时点的机械性痛阈值均较C1组、C3组、C4组明显增加（P<0.05）。与灌胃前比较，C2组大鼠模型灌胃30 min和灌胃后1 h后机械性痛阈值明显升高（P<0.05），但灌胃30 min和灌胃后1 h后的机械性痛阈值无统计学意义（P>0.05）。结论 何首乌可有效降低大鼠的骨癌痛，其有效单体成分是二苯乙烯苷。     

Reliability of a short-term test for hepatocarcinogenesis induced by aflatoxin B1.

The reliability of a short-term test for hepatocarcinogenesis induced by aflatoxin B1 (AFB1) was tested by comparing the early appearance of gamma-glutamyl transpeptidase (GGT)-positive foci with the occurrence of primary liver cancer at a later stage. All rats received a basic short-term treatment with AFB1 intraperitoneally, during which three experimental groups received Chinese green tea or 2000 or 5000 ppm butylated hydroxyanisole in the diet and a control group received basic diet. Some of the rats in each group were sacrificed at the end of the short-term procedure, and the remainder were observed up to 92 weeks. The livers of all animals were examined for GGT-positive foci or primary liver tumours. The GGT-positive foci were most numerous and largest and the incidence of liver tumours was highest in the control group. These findings suggest that GGT-positive foci are a valuable preneoplastic marker for AFB1-induced hepatocarcinogenesis, that the short-term model is fairly reliable, and that both Chinese green tea and butylated hydroxyanisole inhibit AFB1-induced hepatocarcinogenesis.     

Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity

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.     

CDO1通过PI3K/AKT信号通路调控胃癌细胞增殖及细胞周期

目的:探讨半胱氨酸双加氧酶1(CDO1)对胃癌细胞增殖、细胞周期的调控机制。方法:用脂质体法将si-NC组（转染si-NC）、si-CDO1组（转染si-CDO1）、pcDNA组（转染pcDNA）、pcDNA-CDO1组（转染pcDNA-CDO1）、pcDNA-CDO1+DMSO组（转染pcDNA-CDO1并用DMSO处理）、pcDNA-CDO1+IGF-1组（转染pcDNA-CDO1并用IGF-1处理）转染至AKG细胞。用实时荧光定量逆转录聚合酶链反应（qRT-PCR）、免疫印迹（Western blot）、细胞计数试剂盒（CCK-8）、流式细胞术检测细胞CDO1、PI3K、Akt、p-Akt蛋白的表达、细胞增殖、细胞周期。结果:与人胃黏膜上皮细胞GES-1相比，胃腺癌细胞AKG中CDO1的表达明显降低（P<0.05）；与si-NC组相比，si-CDO1组AKG细胞的增殖明显上调，细胞发生明显的S期、G2/M期阻滞，过表达CDO1则具有相反的作用。重要的是，敲减CDO1可上调PI3K/AKT信号通路关键基因PI3K、p-Akt的表达，而过表达CDO1具有相反的作用。激活PI3K/AKT信号通路后，过表达CDO1对胃癌细胞的增殖、细胞周期的调控作用可被部分逆转。结论:CDO1可抑制胃癌细胞的增殖，调控细胞周期，其机制与抑制PI3K/AKT信号通路的活性有关，将为胃癌的治疗提供参考。     

Susceptibility to aflatoxin B1-induced carcinogenesis correlates with tissue-specific differences in DNA repair activity in mouse and in rat

To investigate the mechanisms responsible for species- and tissue-specific differences in susceptibility to aflatoxin B(1) (AFB(1))-induced carcinogenesis, DNA repair activities of nuclear extracts from whole mouse lung and liver and rat liver were compared, and the ability of in vivo treatment of mice with AFB(1) to alter repair of AFB(1)-DNA damage was determined. Plasmid DNA containing AFB(1)-N(7)-guanine or AFB(1)-formamidopyrimidine adducts were used as substrates for the in vitro determination of DNA repair synthesis activity, detected as incorporation of radiolabeled nucleotides. Liver extracts from CD-1 mice repaired AFB(1)-N(7)-guanine and AFB(1)-formamidopyrimidine adducts 5- and 30-fold more effectively than did mouse lung, and approximately 6- and 4-fold more effectively than did liver extracts from Sprague-Dawley rats. The susceptibility of mouse lung and rat liver to AFB(1)-induced carcinogenesis correlated with lower DNA repair activity of these tissues relative to mouse liver. Lung extracts prepared from mice treated with a single tumorigenic dose of 50 mg/kg AFB(1) i.p. and euthanized 2 hours post-dosing showed minimal incision and repair synthesis activities relative to extracts from vehicle-treated mice. Conversely, repair activity towards AFB(1)-N(7)-guanine damage was approximately 3.5-fold higher in liver of AFB(1)-treated mice relative to control. This is the first study to show that in vivo treatment with AFB(1) can lead to a tissue-specific induction in DNA repair. The results suggest that lower DNA repair activity, sensitivity of mouse lung to inhibition by AFB(1), and selective induction of repair in liver contribute to the susceptibility of mice to AFB(1)-induced lung tumorigenesis relative to hepatocarcinogenesis.     

香烟对阻止黄曲霉素B_1诱致小白鼠癌前病变影响的肝细胞核内DNA定量研究

本文将津白2纯系小白鼠60只.随机等数分三组:AFB_1组、AFB_1 香烟熏组和对照组。AFB_1溶于DMSO.5μg/每日/每只量拌于饲料投食,熏烟组以30g/日烟丝熏烟,经半年实验,肝H.E常规切片.发现两实验组.肝细胞有不典型增生,程度难确定,电镜下.肝细胞主要为变质及轻度胶原增生。但肝印片置Leitz MPV Ⅲ型测定肝细胞核DNA含量,发现三组均属多峰型,对照组与AFB_ 烟熏组主峰相当4C处.AFB_1组则在8C处.两实验组间从多倍体与异倍体数量看,则有显著差别(P<0.05).证实AFB_1 烟熏组具有阻止AFB_1诱致小白鼠肝癌变的作用。