Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines

In human breast tissue, estrone (E(1)) and estradiol (E(2)) are mainly hydroxylated by cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) to 2-hydroxyestrogens (2-OHE(1/2)) and 4-hydroxyestrogens (4-OHE(1/2)), respectively. Several studies show that 4-OHE(1/2), but not 2-OHE(1/2), may act as a carcinogen and a high estrogen 4-/2-hydroxylation ratio appears to be a marker for the presence of neoplasms. In this study, we investigated the effects of several dioxin-like compounds on estrogen 2- and 4-hydroxylation in a malignant (MCF-7) and a nontumorigenic (MCF-10A) human mammary epithelial cell line. 2- and 4-methoxyestrogen (MeOE(1/2)) formations were used as measures of the 2- and 4-hydroxylation pathways, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3'4,4',5,5'-hexachlorobiphenyl (PCB 169) concentration dependently induced 2-MeOE(1/2) formation and ethoxyresorufin-O-deethylation (EROD) activity through induced CYP1A1 expression in MCF-7 and MCF-10A cells. 2,3',4,4',5-pentachlorobiphenyl (PCB 118) had no such effect. Effects on CYP1B1 expression and 4-MeOE(1/2) formation were less pronounced; only TCDD caused an induction, whereas PCB 169 was a potent and selective inhibitor of 4-MeOE(1/2) formation (IC(50) 0.7 and 2.2 nM PCB 169 in MCF-7 and MCF-10A cells, respectively). MCF-10A cells were less responsive toward dioxin-like compounds and the apparent EC(50) values for CYP1A1 and CYP1B1 induction in this study were 10-100 fold higher than in MCF-7 cells. The constitutive 4-/2-MeOE(1/2) ratios were 2.99 +/- 0.78 and 0.93 +/- 0.40 in MCF-7 and MCF-10A, respectively. Incubation with dioxin-like compounds resulted in a concentration-dependent decrease in the 4-/2-MeOE(1/2) ratio, but an increase in potentially carcinogenic estrogen metabolites in both MCF-7 and MCF-10A cells. This indicates that even though the 4-/2-OHE(1/2) ratio may be used as indicator for the presence of neoplasms, it is readily lowered by dioxin-like compounds and its value as a prognostic parameter for cancer risk should be further examined.     

K30聚乙烯吡咯啉酮敏化的儿茶酚紫分光光度法测定罐头中锡(Ⅳ)

在 PH2.0·K30聚乙烯吡咯啉酮(PVP)敏化条件下,锡与儿茶酚紫(CV)形成有色化合物,最大吸收波长562nm,摩尔吸光系数7.71×10~7mol~(-1)·cm~(-1),含 Sn 量在0—200ng/100ml 范围内服从比尔定律。分析罐头食品中锡,精密度、准确度和线性关系很好。     

Uncaria tomentosa extracts protect human erythrocyte catalase against damage induced by 2,4-D-Na and its metabolites

The effect of ethanolic and aqueous extracts from leaves and bark of Uncaria tomentosa was studied, with particular attention to catalase activity (CAT – EC. 1.11.1.6).     

The formation of catechol isoquinolines in PC12 cells exposed to manganese

Chronic exposure to manganese causes parkinsonian symptoms and has been implicated as an environmental factor in the pathogenesis of Parkinson's disease (PD). Here we show that manganese inhibits the proliferation of PC12 cells and induces apoptosis through the formation of catechol isoquinolines. Manganese induces the production of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal) and N-methyl-salsolinol (NMSal) in PC12 cells, and increases the levels of malondialdehyde (MDA) in a dose-dependent manner. The data indicates that the formation of catechol isoquinolines due to oxidative stress induced by MnCl(2) may be a mechanism by which manganese causes degeneration of dopaminergic neurons.     

托卡朋治疗帕金森病运动功能波动的临床观察

目的 研究儿茶酚－氧位－甲基转移酶抑制剂（ＣＯＭＴＩ）托卡朋对帕金森病（ＰＤ）患者在复方左旋多巴治疗过程中出现的运动功能波动,如开－关现象,剂末现象,疗效减退,左旋多巴用量减少情况,并观察不良反应,方法 对６９例ＰＤ患者采用多中心自身对照开放方法进行临床观察。应用复方左旋多巴剂量稳定６周后,对符合人入选条件给予托卡朋５０～１００ｍｇ每天３次,１疗程为６周,总的临床观察时间为１２周,结果 托卡朋治疗     

Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

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COMTval158met和OPRM1A118G基因多态性对患者术前疼痛敏感性的影响

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Toxicology of potassium channel-directed compounds in mosquitoes

Potential targets for new vector control insecticides are nerve and muscle potassium channels. In this study, the activities of known potassium channel blockers (4-aminopyridine, quinidine, and tetraethylammonium) and the insecticide propoxur were compared to three experimental catechols and several other compounds against Anopheles gambiae and Aedes aegypti mosquitoes. Experimental catechol 1 was the most toxic experimental compound in all of the mortality assays conducted, but was at least 100-fold and 39-fold less toxic than propoxur against Ae. aegypti and An. gambiae, respectively. Injection treatment and synergist (piperonyl butoxide) bioassays found that catechol toxicity was not unduly impacted by cuticular transport or oxidative metabolism. Electrophysiological studies showed a decrease in amplitude of evoked muscle contractions, along with an increase in twitch duration at concentrations that increased basal muscle tension (mM). High concentration effects on basal muscle tension were matched by complete depolarization of the muscle membrane potential. Effects on muscle physiology and blockage of Kv2.1 potassium channels in patch clamp experiments were generally consistent with in vivo toxicity, except for 4-aminopyridine, which suggest the involvement of other potassium channel subtypes. Extensive melanization of Anopheles larvae, but not Aedes larvae, occurred from exposure to catechol compounds. Interaction with the phenol oxidase system within insects may be the cause of this melanization, but any contribution to toxicity requires further investigation.     

抑郁症患者红细胞儿茶酚氧位甲基转移酶活性的研究

目的探讨抑郁症患者红细胞儿茶酚氧位甲基转移酶(COMT)活性及其与抑郁症发病机制的可能联系。方法采用高效液相色谱法测定110例抑郁症患者(其中单相42例,双相68例;患者组)和120名健康人(对照组)红细胞COMT的活性浓度,对测定结果进行对照比较。结果患者组男女之间、对照组男女之间,单、双相抑郁两组间的红细胞COMT活性浓度的差异均无统计学意义(P>0.05)。患者组的红细胞COMT活性频率分布在2～23μmol·LRBC-1·h-1,其中在11μmol·LRBC-1·h-1附近分布最高;对照组分布在7～28μmol·LRBC-1·h-1,其中在16μmol·LRBC-1·h-1附近分布最高。患者组的红细胞COMT平均活性浓度为(11.0±3.7)μmol·LRBC-1·h-1,其中男性患者COMT活性浓度为(11.2±3.5)μmol·LRBC-1·h-1,女性患者为(10.6±4.0)μmol·LRBC-1·h-1。对照组的红细胞COMT平均活性浓度为(16.1±4.3)μmol·LRBC-1·h-1,其中男性为(16.5±4.6)μmol·LRBC-1·h-1,女性为(15.4±3.9)μmol·LRBC-1·h-1,患者组与对照组以及两组同性别之间的红细胞COMT活性浓度的差异均有统计学意义(均P<0.01)。结论抑郁症患者的红细胞COMT活性浓度低于正常,抑郁症的发病机制可能与血浆红细胞中COMT活性浓度降低有关。     

精神分裂症患者儿茶酚胺氧位甲基转移酶基因单核苷酸多态位点与利培酮疗效的关联研究

目的 分析利培酮治疗首次发病(以下简称首发)的精神分裂症患者疗效与儿茶酚胺氧位甲基转移酶(COMT)基因多态性的关联,探讨利培酮疗效的敏感基因.方法 对203例首发精神分裂症患者给予利培酮治疗8周(2～8 ms/d),分别于治疗前和治疗第2～8周末采用阳性和阴性症状量表(PANSS)评分,以减分率评定疗效.并采用限制性片段长度多态技术和序列特异性引物聚合酶链反应技术测定基因型.对痊愈组(29例)、进步组(153例)及无效组(21例)精神分裂症患者与COMT基因单核苷酸多态位点(SNPs)进行关联分析.结果 COMT基因3种多态性基因型及基因频率在利培酮不同疗效患者组间分布差异均无统计学意义(P均＞0.05).COMT的3个单核苷酸多态位点单体型分析,利培酮治疗痊愈组与进步组、有效组与无效组间的差异无统计学意义(P＞0.05).结论 COMT基因可能不是首发精神分裂症患者抗精神病药利培酮的疗效敏感基因.