饮茶对香烟中特异性亚硝胺－NNK诱发小鼠肺癌基因表达的影响

通过研究饮茶对香烟中特异性亚硝胺－ＮＮＫ诱发小鼠肺癌基因表达的影响，对饮茶可拮抗香烟致癌作用的结果做进一步验证，并对其作用机理进行探讨。所使用方法为国内外尚属新的技术，即非同位素标记探针测定基因表达。其结果表明阳性小鼠给ＮＮＫ４周后，ｃ－ｍｙｃ和ｃ－ｒａｆ基因表达水平明显增高，而小鼠若同时饮绿茶则可抑制这种增高，抑制率达５０％和２０％，到第８周时阳性对照组的ｃ－ｍｙｃ和ｃ－ｒａｆ基因水平恢复正常。与此相对应，ｃ－Ｈ－ｒａｓ基因在第８周时表达增高，约为阴性组３倍，饮茶对此同样有抑制作用，抑制率为５０％。在第２、４和８周均未见阳性对照组ｖｓｉｓ基因表达水平的改变。     

茶对促癌物（TPA）诱发小鼠皮肤癌基因表达的影响

通过研究在小鼠皮肤上涂抹儿茶素ＥＧＣＧ对促癌物（ＴＰＡ）诱发小鼠皮肤组织某些癌症发生有重要关系的基因（ｃ－ｍｙｃ，ＯＤＣ、蛋白激酶Ｃ即ＰＫＣ基因）表达水平的影响，对茶叶抗皮肤癌的机制做了较深入的探讨。其结果表明阳性小鼠皮肤涂１０ｎｍｏｌＴＰＡ４ｈ后，上皮组织中ＯＤＣ基因表达水平比阴性组高出４．５倍，而ＥＧＣＧ对其有明显的抑制作用，１μｍｏｌ和５μｍｏｌＥＧＣＧ剂量组的抑制率分别为１６％和５６％，有一定的剂量－反应关系。Ｃ－ｍｙｃ与ｐＫＣ基因表达水平在阳性组也有明显的升高，分别为５．０和１．９倍，ＥＧＣＧ同样具有抑制作用，５μｍｏｌ的抑制率分别为２４％和２１％。     

接触苯工人白细胞癌基因激活的研究

应用ＰＣＲ－Ｂｌｏｔ和Ｄｏｔ－Ｂｌｏｔ技术检测了１０３名接触苯工人和７０名对照组工人外周血白细胞ｃ－Ｋｉ－ｒａｓ２基因和ｃ－ｍｙｃ基因。结果表明，１０３名接苯者中有４例其外周血白细胞检出ｃ－Ｋｉ－ｒａｓ２基因１２位点Ｇ→Ｔ突变，其接苯工龄在６～１０年，而７０名对照者未检出该突变；ｃ－Ｋｉ－ｒａｓ２基因１２位点（Ｇ→Ａ突变在两组工人中均未检出阳性；ｃ－ｍｙｃ基因亦未在两组工人中检出扩增现象。结果提示，ｃ－Ｋｉ－ｒａｓ２基因１２位点Ｇ→Ｔ突变与慢性接触苯有关，有可能是苯白血病发生的分子机理。     

苯并芘诱发人肺癌细胞系（BT）的染色体异常及myc，p53及Rb基因研究

本文对由致癌物苯并芘诱发的人肺癌建立的细胞系（ＢＴ）进行了染色体分析及ｍｙｃ，Ｒｂ和ｐ５３基因研究。发现许多异常染色体，以３号，５号，１１号，１３号，１７号染色体改变较多，对定位于这些染色体上的Ｈａ－ｒａｓ，ｒａｆ－１，ｐ５３，Ｒｂ和ｃ－ｍｙｃ的表达、扩增及重排情况进行了分析，发现ｃ－ｍｙｃ，ｐ５３，Ｒｂ三个基因发生了改变，说明染色体异常导致的基因改变与苯并芘诱发人肺癌的发生机制可能密切相关。     

上皮性卵巢肿瘤C—myc与p53蛋白的表达及意义

用免疫组化ＬＳＡＢ方法检测５例正常卵巢组织和３５例卵巢肿瘤组织中的Ｃ－ｍｙｃ（原癌基因）和ｐ５３（抑癌基因）蛋白的表达水平。结果从良性卵巢腺瘤、交界性到恶性卵巢囊腺癌，Ｃ－ｍｙｃ和ｐ５３阳性表达呈增高趋势。其阳性表达率与卵巢肿瘤的细胞增殖状态、肿瘤分化及临床分期有关。检测卵巢肿瘤中Ｃ－ｍｙｃ及ｐ５３基因表达可了解卵巢囊腺癌的发生、发展，找出原癌基因及抑癌基因表达与卵巢瘤生物学行为间的关系。     

链霉素对缺氧大鼠右心室肥大及C－myc原癌基因表达的影响

本文观察了非选择性阳离子通道阻断剂链霉素（在脊椎动物心肌阻断牵张激活的钠离子跨膜内流）对缺氧大鼠右心室肥大和缺氧大鼠心肌中ｃ─ｍｙｃ基因表达的影响。结果如下：（１）急性缺氧时，右心室收缩压明显增高，慢性间断性缺氧进一步增高右心室收缩压并明显增高右心室重量指数。（２）链霉素对急性缺氧性肺动脉增压反应无影响，但可明显降低慢性缺氧大鼠右心室收缩压和右心室重量指数。（３）缺氧引起右室心肌迅速一过性的ｃ－ｍｙｃ基因表达增强，链霉素可降低ｃ－ｍｙｃ表达水平。提示Ｎａ内流和Ｃ－ｍｙｃ表达可能参与了缺氧性右心室肥大的发生。     

镉对小鼠肢芽细胞增殖细胞核抗原和c—myc基因表达的影响

目的探讨镉对胚胎肢芽细胞增殖抑制的机制。方法运用免疫组化ＳＰ法结合图像分析技术观察了ＣｄＣｌ２对增殖细胞核抗原（ＰＣＮＡ）和ｃ－ｍｙｃ基因表达的影响。结果ＰＣＮＡ和ｃ－ｍｙｃ基因在正常增殖的胚胎肢芽细胞中均呈强阳性免疫反应；０．１～０．８μｇ／ｍｌＣｄＣｌ２对细胞中ＰＣＮＡ和ｃ－ｍｙｃ的表达均有明显的抑制作用，并呈现明显的剂量－效应关系。结论ＣｄＣｌ２可通过抑制ＰＣＮＡ和ｃ－ｍｙｃ的表达而对胚胎细胞增殖产生抑制作用。     

甲基叔丁基醚对原癌基因和功能基因表达的影响

甲基叔丁基醚（ＭＴＢＥ）是一种新型的汽油添加剂,被用来提高汽油燃烧效率,减少汽车尾气中有害物质的排放。ＭＴＢＥ具有一定的动物致癌性,但其机制目前并不清楚。本研究采用免疫组织化学方法,检测了ＭＴＢＥ对体外培养的ＮＩＨ３Ｔ３细胞中ｃ－ｍｙｃ和ｐ２１蛋白表达的影响;采用点杂交方法,从ＲＮＡ水平检测了ＭＴＢＥ亚慢性染毒大鼠肝组织中原癌基因ｃ－ｍｙｃ基因和功能基因ＧＳＴ－Ｐ基因的表达情况。免疫组化结果显示,ＭＴＢＥ可诱导ｃ－ｍｙｃ基因的高表达,对ｐ２１蛋白的表达未见明显影响。点杂交结果显示,ＭＴＢＥ可明显诱导大鼠肝组织中ｃ－ｍｙｃ基因的高表达,而对ＧＳＴ－Ｐ基因的表达未见明显影响。上述结果提示,ＭＴＢＥ可诱导细胞中ｃ－ｍｙｃ基因表达活性增高,可能是其动物致癌性的机制之一。     

茶对小鼠免疫功能的保护作用

目的探讨茶叶防癌的免疫调节机理。方法用致癌剂４甲基亚硝胺１（３吡啶）１丁酮（ＮＮＫ）诱发小鼠肿瘤的实验模型，观察ＮＮＫ所致小鼠免疫功能的改变及绿茶（ＧＴ）、复合茶（ＭＴ）和茶多酚（ＴＰ）的保护作用。结果小鼠注射ＮＮＫ后，在观察的４周内，腹腔巨噬细胞吞噬功能、外周血白细胞化学发光、迟发型变态反应、脾细胞抗体生成细胞数、以及脾ＮＫ活性等免疫指标，与正常对照组比较均出现不同程度的增高或降低；而ＧＴ、ＭＴ和ＴＰ对所有这些免疫功能的不良改变有明显的保护作用。结论茶及其成分对ＮＮＫ诱发小鼠肿瘤过程中早期所致免疫功能的改变具有保护作用     

甲基叔丁基醚对大鼠肝组织基因表达的影响

目的甲基叔丁基醚（ＭＴＢＥ）是一种新型的汽油添加剂,动物试验显示其具有一定的致癌性。为了解其动物致癌性的可能机制,我们检测了经ＭＴＢＥ亚慢性染毒的大鼠肝组织中原癌基因ｃｍｙｃ基因和功能基因谷胱甘肽Ｓ转移酶Ｐ（ＧＳＴＰ）基因的表达情况。方法４０只雄性ＳＤ大鼠,体重１８０～２００ｇ,随机分为４组。将ＭＴＢＥ溶于适量豆油中,灌胃染毒,染毒剂量分别为２００ｍｇ／ｋｇ,６００ｍｇ／ｋｇ,１０００ｍｇ／ｋｇ和对照组。每天１次,每周５天,共１３周。动物肝组织于液氮速冻后,一步法提取总ＲＮＡ。随机引物法地高辛标记ｃｍｙｃ和ＧＳＴＰ探针,与ＲＮＡ进行点杂交,图像分析仪分析结果。结果大鼠肝组织中ｃｍｙｃ基因表达水平明显增高,ＧＳＴＰ基因表达未见增强。结论ＭＴＢＥ可明显诱导ｃｍｙｃ基因的高表达,提示其具有促进细胞增殖的作用,这是其动物致癌性的可能机制之一。     

4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮接触生物标志物的研究进展

4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮(NNK)是烟草特有亚硝胺(TSNA)中具有强烈致癌性的物质之一,NNK在人体和动物体内产生的主要代谢物是4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁醇(NNAL)和它的糖苷化合物(NNAL-N-Glucuronidec和NNAL-O-Glucuronide).NN...     

烟草特有亚硝胺的致癌作用及其抑制

该文综述了烟草特有亚硝胺4-(N-亚硝基甲氨基)-1-(3-吡啶基)-1-丁酮(NNK)的致癌作用及其抑制方面的研究进展,羰基还原和α-羟基化是NNK代谢活化的主要途径,NNK致癌主要作用器官是肺,致癌可能性与个体有关.有机异硫氰酸盐是NNK致癌的强抑制剂.多食用十字花科蔬菜、多吃水果、多饮用绿茶和黑茶对吸烟者和被动吸烟者是有益的.     

Synthesis and characterization of the Zn(II) and Cu(II) piperidinyl isoeuxanthone complexes: DNA-binding and cytotoxic activity

Two new complexes ZnL₂·2H₂O (1) and CuL₂·2H₂O (2) (HL = 1-hydroxy-6-(2-(1-piperidinyl)ethoxy)xanthone) have been synthesized and characterized. Their interactions with calf thymus DNA (ct DNA) were investigated by absorption spectroscopy, fluorescence spectroscopy, ethidium bromide (EB) displacement experiments, circular dichroism spectroscopy and viscosity measurements. Experimental results suggested that there were intercalative interactions of the complexes with DNA. The binding affinity of complex 2 was higher than that of 1. In addition, the cytotoxic effects of both complexes were evaluated with lung adenocarcinoma (GLC-82), esophagus squamous cancer (ECA109) and human gastric cancer (SGC7901) cells using MTT assay. Both were potent exhibiting significant cytotoxicity in vitro.     

1,25-(OH)2D3抑制人肝癌细胞增殖的研究

目的：探讨1，25－（OH）2D3抑制肝癌细胞增殖的机制。方法：体外培养肝癌细胞株SMMC－7721，培养基因10、50及100（nmol/L)1，25－（OH）2D3作用2d,4d,6d后，用四唑盐比色试验（MTT）和平板克隆形成实验检测细胞的存活和生长；台盼蓝拒染法绘制生长曲线；DNA凝胶电泳检测肝癌细胞凋亡。结果：MTT和平板克隆形成实验检测结果显示10－100nmol/L的1，25－（OH）2D3均对SMMC－7721细胞株有显的抑制作用，且呈剂量－效应关系。DNA凝胶电泳结果显示，1，25－（OH）2D3能够诱导SMMC－7721细胞凋亡。结论：1，25－（OH）2D3对于人肝癌细胞株SMMC－7721的增殖有显的抑制，其机理可能是通过干扰肝癌细胞的DNA代谢和诱导肝癌细胞凋亡。     

右旋反式氯丙炔菊酯的合成及其药效研究

目的研制一种新型卫生杀虫剂--右旋反式氯丙炔菊酯.方法采用右旋反式DV菊酸与S-炔丙醇酮为原料,经化学拆分、酰氯化及酯化等反应合成右旋反式氯丙炔菊酯,并采用GB/T13917.1-1992和GB/T17322.2-1998标准方法测定了对致倦库蚊和德国小蠊的药效.结果右旋反式氯丙炔菊酯对致倦库蚊及德国小蠊的KT50值分别为8.5 min和3.46min.结论右旋反式氯丙炔菊酯对蚊虫和蟑螂等害虫具有良好的击倒作用和杀灭能力,可以作为一种新型卫生杀虫剂加以推广和应用.     

ROLE OF PHOSPHATE ON VITAMIN D ACTION IN CHICK ILEUM ORGAN CULTURE

It is postulated that the primary action of vitamin D sterols in the intestine is to enhance the ability of the mucosal cell to accumulate phosphate.     

Synthesis, characterization and antibacterial activity of 2-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazol-4-yl]-5-(substituted-phenyl)-[1,3,4]oxadiazoles

In the present investigation a series of novel 2-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazol-4-yl]-5-(substituted-phenyl)-[1,3,4]oxadiazoles (4a–j) were synthesized by cyclization of substituted-benzoic acid N′-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-hydrazide by using phosphorousoxychloride at 120 °C. The chemical structure of the newly synthesized compounds was characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR and LC–MS) methods. The title compounds were screened for qualitative (zone of inhibition) and quantitative antibacterial activity (MIC) by agar cup plate and microtitration methods, respectively. Among the synthesized compounds in this series compound 2-[1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl]-5-(4-fluorophenyl)-1,3,4-oxadiazole (4b) was found to exhibit significant antibacterial activity with MICs of 22.4, 29.8, 29.6 and 30.0 μg/mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, respectively. The other compounds exhibited moderate activity when compared to standard substance Ampicillin.     

Identification of methylene diphenyl diisocyanate thermal degradation products in a generation chamber by liquid chromatography coupled with tandem mass spectrometry

Isocyanate thermal degradation characterization by liquid chromatography coupled with electrospray tandem mass spectrometry has been performed to elucidate the methylene diphenyl diisocyanate (MDI) thermal degradation structure emitted in a generation chamber using a temperature between 50°C and 180°C to produce MDI vapors. [M+H]⁺ ions containing an isocyanate functional group were studied by tandem mass spectrometry. The [M+H]⁺ ion analyses based on the combination of full scans and precursor ion scans were useful for identifying all structures. The compounds emitted were identified and validated as a mixture of compounds containing amine and isocyanate functions. Residual MDI, methylene diphenyl amino-isocyanate, and methylene diphenyl diamine were identified. Polymerized forms of these structures were also observed because amine and isocyanate chemical functions react rapidly to polymerize. These results must be used with special care by scientists establishing sensitization diagnostics and developing sampling devices using generation chambers as they must be related to MDI behavior in workplaces. Even if pure MDI is introduced in the generation chamber, several different compounds are generated when the MDI is heated at a high temperature. This can result in some misleading interpretations for non-specific isocyanate sampling device development and sensitization diagnostics as MDI is present in the chamber with other compounds with known adverse effects.     

Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the dominant "protective" immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and cells. The results showed marked differences in the fine specificity among these mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and GT3 carbohydrates, representing structures found on surfaces of neural and developing cells, were demonstrated using carbohydrate array technology. The anti-CPS(III) mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we serendipitously demonstrated cross-reactions of some anti-CPS(III) mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen.