Factors associated with plasma concentrations of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p’-DDE) in the Canadian population

This study describes blood plasma concentrations of PCBs and p,p’-DDE in the Canadian population aged 20–79 years. PCBs and p,p’-DDE were measured in 1668 participants in the Canadian Health Measures Survey, Cycle 1 (2007–2009). We investigated how concentrations vary by sociodemographic, anthropometric, and lifestyle variables, identified factors associated with exposures, and evaluated concentrations against health-based guidance values. Congeners of PCB most commonly detected were PCB-138, PCB-153, and PCB-180. p,p’-DDE was detectable in > 99% of the samples. Factors associated with ∑PCBs were age, region of birth, frequency of fish consumption, and liver intake (R² = 58.1%). For p,p’-DDE, significant factors were sex, age, region of birth, household education, and ethnic origin (R² = 47.0%). PCB concentrations in Canadians were similar to those in the United States, and lower than those reported in Europe. A small percentage equalled or exceeded the Human Biomonitoring value of 3.5 µg/L for PCBs. Few exceedances of the p,p’-DDE biomonitoring equivalent were observed.     

CDKN2A位点p16~(INK4α)、p14~(ARF)基因变异与胃癌发生的关系

目的 探讨p16~(INK4a)和p14~(ARF)基因变异与胃癌发生的关系。方法 应用聚合酶链反应(PCR)、PCR-单链构象多态性(SSCP)、PCR甲基化分析法和RT-PCR分别检测48例胃癌及癌旁组织中p16~(INK4a)和p14~(ARF)基因纯合性缺失、突变、CpG岛甲基化及mRNA表达状况。结果(1)胃癌组织p16~(INK4a)和p14~(ARF)基因总缺失率为35.4％(17/48),癌旁组织均未见纯合性缺失。(2)31例无纯合性缺失的胃癌及癌旁组织均未见p16~(INK4a)和p14~(ARF)基因点突变。(3)胃癌组织p16~(INK4a)和p14~(ARF)基因总甲基化率为47.90％(23/48),癌旁组织仅2例甲基化,两者差异有显著性(P<0.01)。(4)胃癌组织p16~(INK4a)mRNA缺失率为47.9％(23/48),其中E1α和E2共甲基化者p16~(INK4a)mRNA缺失率(100％,6/6)明显高于其他类型甲基化者(11.8％,2/17)(P<0.01);胃癌组织p14~(ARF)mRNA缺失率为45.8％(22/48),其中E1β和E2共甲基化者p14~(ARF)mRNA缺失率(100％,3/3)明显高于其他类型甲基化者(15％,3/20)(P<0.05)。(5)低未分化癌组p16~(INK4a)和p14~(ARF)mRNA共同缺失率(36.7％,11/30)明显高于高中分化癌组(5.6％,1/18)(P<0.05)。结论 胃癌中p16~(INK4a)和p14~(ARF)基因失活多由纯合性缺失和5’CpG岛甲基化所致,其表达缺失与胃癌的发生密切相关。     

人类肝细胞癌(HCC)时CpG广泛甲基化灭活p16~(INK4)表达

免疫组化证实６０例ＨＣＣ中有２９例ｐ１６ＩＮＫ４表达完全丧失,在２９例ｐ１６ＩＮＫ４表达完全丧失者中,有２４例ＣｐＧ硷基甲基化高达６０～８５％。相反在ｐ１６ＩＮＫ４染色较浅的肿瘤组织内甲基化水平低于２５％,在ｐ１６ＩＮＫ４染色阳性反应肿瘤组织内则未能检出ＣｐＧ的甲基化。因而肿瘤组织内ＣｐＧ甲基化水平反映ｐ１６ＩＮＫ４表达程度。上述结果表明,ＨＣＣ细胞内ＤＮＡ大量的甲基化,致使ｐ１６ＩＮＫ４表达灭活,终至发生基因表型改变。港澳台医讯：据１９９９年《美国外科年鉴（ＡＮＮＡＬＳＯＦＳＵＲ－ＧＥＲＹ,２…     

Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males

Background: Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized.Objectives: In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 to < 17 years of age with documented toxicant exposures.Methods: Data were collected between February 1996 and January 2000. Fasting blood specimens were collected before breakfast by trained Akwesasne Mohawk staff. Multivariable regression models were used to estimates associations between toxicants and serum testosterone, adjusted for other toxicants, Tanner stage, and potential confounders.Results: The sum of 16 PCB congeners (Σ16PCBs) that were detected in ≥ 50% of the population was significantly and negatively associated with serum testosterone levels, such that a 10% change in exposure was associated with a 5.6% decrease in testosterone (95% CI: –10.8, –0.5%). Of the 16 congeners, the more persistent ones (Σ8PerPCBs) were related to testosterone, whereas the less persistent ones, possibly reflecting more recent exposure, were not. When PCB congeners were subgrouped, the association was significant for the sum of eight more persistent PCBs (5.7% decrease; 95% CI: –11, –0.4%), and stronger than the sum of six less persistent congeners (3.1% decrease; 95% CI: –7.2, 0.9%). p,p´-DDE was positively but not significantly associated with serum testosterone (5.2% increase with a 10% increase in exposure; 95% CI: –0.5, 10.9%). Neither lead nor HCB was significantly associated with testosterone levels.Conclusions: Exposure to PCBs, particularly the more highly persistent congeners, may negatively influence testosterone levels among adolescent males. The positive relationship between p,p´-DDE and testosterone indicates that not all POPs act similarly.Citation: Schell LM, Gallo MV, Deane GD, Nelder KR, DeCaprio AP, Jacobs A; Akwesasne Task Force on the Environment. 2014. Relationships of polychlorinated biphenyls and dichlorodiphenyldichloroethylene (p,p´-DDE) with testosterone levels in adolescent males. Environ Health Perspect 122:304–309; http://dx.doi.org/10.1289/ehp.1205984     

Disposition of β-hexachlorocyclohexane,p,p′-DDT,and trans-chlordane administered subcutaneously to monkeys (Macaca fascicularis)

To evaluate skin lipid analysis for the accumulation level of environmental pollutants, the correlations between organochlorine pesticide residues in adipose tissue, blood, and skin lipids of monkeys were studied. The mixture of -hexachlorocyclohexane (-HCH), p,p-DDT, and trans-chlordane was subcutaneously given to monkeys once weekly for 5 weeks at dose levels of 1 and 10 mg/kg. The chemicals distributed in adipose tissue, blood, and skin lipids were determined six times after the last dosing at intervals of 4 to 9 weeks.Oxychlordane and p,p-DDE were detected in all tissues together with the administered chemicals. In blood and adipose tissue, trans-chlordane decreased rapidly and oxychlordane and p,p-DDE increased gradually and then remained at constant levels. -HCH and p,p-DDT in adipose tissue increased until the 12th week and then decreased in all animals. The correlation coefficients between blood and adipose tissue regardless of dose level and collection time for each chemical ranged from 0.83 to 0.94. Correlation coefficients between skin lipids and adipose tissue varied with the chemical, namely, 0.31, 0.72, 0.81, 0.81, and 0.83 for p,p-DDE, tras-chlordane, p,p-DDT, -HCH, and oxychlordane, respectively. The results indicated that skin lipid analysis may be useful for the evaluation of specific pollutants in the body burden.     

p73在苯并(a)芘致人肺纤维细胞株MRC-5和人肺腺癌细胞株H1299(p53-null)周期阻滞中的作用

目的 研究p73在苯并(a)芘[B(a)P]致人肺纤维细胞株MRC-5和人肺腺癌细胞株H1299(p53-null)周期阻滞中的作用.方法 采用0(溶剂对照)、8、16、32、64和128 μmol/L的B(a)P分别处理处于对数生长期的MRC-5和H1299细胞24 h.采用MTT比色法检测两种细胞系的生长率,采用流式细胞术检测细胞周期各时相的细胞百分比,采用实时荧光定量PCR方法测定p53,p73,p21和Gadd45的mRNA表达水平.结果 与溶剂对照组比较,8、16、32、64μmol/L B(a)P染毒组MRC-5细胞和H1299细胞的增殖活性均升高,差异有统计学意义(P＜0.05或P＜0.01).16μmol/L B(a)P染毒组MRC-5细胞和32 μmol/LB(a)P染毒组H1299细胞的增殖活性达到峰值,与溶剂对照组相比,分别增加了40%和30%.与溶剂对照组比较,8、16、32、64和128μmol/L的B(a)P染毒组MRC-5细胞的p53.p73和p21基因mRNA表达水平上升,差异均有统计学意义(P＜0.05或P＜0.01),细胞阻滞在G1期.与溶剂对照组比较,8 μmol/L的B(a)P染毒组H1299细胞p73和p21基因mRNA表达的表达水平上升,差异均有统计学意义(P＜0.05),细胞阻滞在G1期;但各处理组Gadd45基因的mRNA表达水平间比较,差异无统计学意义(P＞0.05).结论 一定浓度B(a)P可通过p53介导引起MRC-5细胞周期G1期阻滞,而对于p53缺失的H1299细胞,其细胞周期G1期阻滞可能依赖于p73参与的细胞信号通路的调节.     

p16~(INk4A)在宫颈癌早期及癌前病变中的表达

目的:探讨p16INK4A在宫颈癌早期及癌前病变中的表达,以及临床、病理分级间的相关性,寻找一种发现宫颈癌早期及癌前病变的新途径。方法:应用免疫组织化学方法(S-P法)检测p16INk4A在30例正常宫颈组织、40例慢性宫颈炎、100例宫颈上皮内瘤样病变(CIN)及107例宫颈鳞癌中的表达。结果:p16INk4A在上述五种组织中均有表达,且表达阳性率逐渐降低,分别为93.33%、90.00%、60.00%、44.86%,且其表达与宫颈癌病理分级、临床分期、淋巴转移有关。结论:p16INk4A的表达与宫颈癌的发生、发展有关,p16INK4A不仅为细胞周期的固有调控者,亦有可能在其他方面影响细胞生物学行为。     

p16基因异常甲基化与结肠癌发生及诊治的关系(综述)

一、p16基因的特点及功能。p16基因，或称多肿瘤抑癌基因1(MTS1)，CDK抑制因子2(CDKN2)，是新发观的一个重要抑癌基因，其频繁的突变率和强大抑癌作用引起了肿瘤分子生物学、分子遗传学等多领域专家学者的广泛关注。目前公认p16基因通过其编码的p16蛋白抑制细胞过度分裂而抑制癌症形成。正常机体细胞内存在促细胞增殖与抑制其增殖的两种平衡体系，促增殖系统成分的过度表达或抑制增殖系统成分的缺失。都会造成细胞增殖失控导致癌变。CDK4为促增殖成分。它与cyclin D结合后被活化，使RB基因磷酸化失活，失去对细胞分裂所需酶的合成抑制作用。p16基因编码的p16蛋白则为CDK的抑制剂，可竞争性结合CDK4，保护RB基因不被磷酸化，阻止细胞由G1期进入S期，表观出抑制细胞过度分裂的抑癌作用。     

细胞周期调控基因p21~(WAF1/CIP1)与宫颈癌

p21WAF1/CIP1基因是1993年发现并克隆的细胞周期依赖性蛋白激酶抑制因子(Cyclin-dependent kinas inhibitor,CDKI)的家族成员,与p21ras不同,它参与细胞的多种功能活动。近年的许多研究表明,p21WAF1/CIP1基因与宫颈癌的发生、发展关系密切,从而引起学者的关注。1p21WAF1/CIP1基因的发现与命名p21WAF1/CIP1基因是在不同实验室用不同的方法克隆出来的。Harper等〔1〕从细胞周期出发寻找CDK调节蛋白时,发现一种可与细胞周期依赖性蛋白激酶(cyclin-depedent kinase,CDK)相互作用的蛋白,并将其克隆,命名为CDK相互作用蛋白(cyclin-…     

NF-κB(p50/p65)介导的促炎微小RNA信号转导在金黄色葡萄球菌感染中的作用

目前已经在金黄色葡萄球菌感染中鉴定并部分表征了NF-κB(p50/p65)调节的微小RNA (miRNA), miRNA包括miR-125b、miR-193b-5p、miR-128、miR-146a、miR155、bta-miR-223和miR-30a。试验结果显示, 在金黄色葡萄球菌感染性疾病中, 这种促炎性miRNA家族的上调协调了致病性基因表达, 为阐述金黄色葡萄球菌感染机制、疾病的传播和严重程度提供了新的可能。本文就当前研究领域涉及NF-κB调节miRNA介导的信号传导途径, 以及针对NF-κB和/或促炎性miRNA信号传导的治疗策略进行综述, 为后续相关研究提供参考。     

分子细胞遗传学结合临床特征产前诊断1例新生儿具rec(7)dup(7q)inv(7)(p22 q31.3)pat核型

某一染色体的部分重复或缺失,让我们有机会观察到获得或丢失某些特殊遗传物质后的表现型。运用分子细胞遗传学分析,于产前诊断1例父源性的减数分裂重组后导致7p22远端丢失和7q31.3-qter的重复。因为娩下一活婴,故可以结合产前的超声检查和产后的临床表现来明确细胞遗传学的异常。 孕妇30岁,白种人,孕2产1。孕20周时当地B超怀疑胎儿脊椎畸形就诊。B超发现胎儿L_2、L_3水平呈半脊椎畸形,颈部皮肤折     

宫颈鳞癌中p33~(ING1b)与Syk基因表达及临床意义

目的探讨p33ING1b与Syk基因在宫颈鳞癌中的表达及临床意义。方法采用免疫组化S-P法检测60例宫颈鳞癌及其相应的癌旁组织中p33ING1b、Syk的基因蛋白的表达。结果宫颈鳞癌组织中的p33ING1b和Syk的表达均低于宫颈癌旁组织;在有淋巴转移和低分化的宫颈鳞癌组织中的表达,要低于无淋巴转移和高分化的宫颈鳞癌组织,差异有统计学意义(p<0.05)。与FIGO宫颈癌分期无关(p>0.05)。结论在宫颈鳞癌组织中p33ING1b和Syk的表达降低或缺失,与宫颈鳞癌的发生、发展和转移有关,对判断宫颈鳞癌的预后和浸润转移潜能有一定的参考价值。     

冠心病与NAD(P)H氧化酶p22phox基因C242T多态性

目的探讨烟酰胺腺嘌呤二核苷酸磷酸盐氧化酶[NAD(P)H氧化酶]p22phox基因C242T多态性与冠心病的关系。方法采用病例对照研究方法,收集早发冠心病患者309例,迟发冠心病患者437例,对照470例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因分型技术对p22phox基因C242T位点的多态性进行检测;采用单因素和多因素logistic回归计算p22phox基因C242T多态性与冠心病风险的OR值及95%CI。结果与对照组比较,早发冠心病组携带TC+TT基因型的个体比携带CC基因型更容易患冠心病,OR=1.58,95%CI=1.07～2.34;迟发冠心病组OR=1.48,95%CI=1.03～2.13;多因素调整后,与对照组比较,早发冠心病组OR=1.74,95%CI=1.16～2.62;2个病例组比较,携带TC+TT基因型与携带CC基因型的患病风险差异均无统计学意义。结论p22phox基因C242T多态性的T等位基因可能是冠心病的危险因素。     

Metabolism and storage ofp,p′ dicofol in American kestrels (Falco sparverius) with comparisons to Ring Neck Doves (Streptopelia risoria)

Residues ofp,p dicofol,p,p dichlorobenzophenone (p,p DCBP),p,p dichlorobenzhydrol (p,p DCBH), 1,1-bis (4-chlorophenyl)-2,2-dichloroethanol (p,p DCD) and 1,1-bis (4-chlorophenyl)-2,2 dichloroethylene (p,p DDE) are reported in liver, fat, brain and oviducts of American kestrels exposed top,p dicofol. Breeding female kestrels were exposed to oral gavage dosages of 3.0 and 0.3 mg dicofol/kg body weight per day, equivalent to 1 or 10 mg dicofol/kg diet, for 39 days. Kestrels exhibited an eggshell thinning response similar to that produced by DDE, under these exposures. The major hepatic metabolite of dicofol in kestrels was DCD, but most organochlorine stored in tissues was in the form of dicofol. DDE was not a major metabolite of dicofol in kestrels. Compared with doves, kestrels had a significantly reduced metabolic capacity to transform dicofol to DCBP and DCBH, and had a steeper dose-response curve for dicofol-induced eggshell thinning.     

p53蛋白在苯并(a)芘诱导的p21、E2F-1表达及细胞周期改变中的作用

目的 探讨p53蛋白在苯并(a)芘[benzo(a)pyrene,B(a)P]诱导的人胚肺成纤维细胞(HELF)细胞周期改变中的作用及其与p21、E2F-1的关系.方法 转染p53 siRNA质粒(p53-H)和载体CMV的HELF细胞(HELF/CMV)无血清培养48 h后,加入2 μmol/L B(a)P作用24 h.用流式细胞仪检测细胞周期的变化.用Western blotting检测细胞中p53、p21蛋白含量的改变,利用细胞核、细胞浆分离技术观察其亚细胞定位.用免疫荧光法观察E2F-1蛋白含量及细胞核、细胞浆分布.利用p53 siRNA质粒和化学抑制剂pifithrin-α(PFT)抑制其表达,观察p53与p21、E2F-1的上下游关系以及其在B(a)P引起的细胞周期改变中的作用.结果 2 μmol/L B(a)P作用24 h后,G1期细胞比例由(71±5)%减少为(39±4)%;p53、p21以及E2F-1蛋白含量增加,并且主要分布在细胞核内.用p53 siRNA质粒和PFT抑制p53表达后,B(a)P诱导的p21高表达被抑制,细胞核内的含量明显减少;B(a)P诱导的E2F-1蛋白含量增加以及细胞周期的改变没有明显变化.结论 B(a)P通过p53非依赖的信号通路引起HELF细胞周期的改变;p53对p21的表达具有调节作用,而对E2F-1的表达不具有调节作用.     

p57~(kip2)和PCNA蛋白在西宁地区食管鳞癌中的表达

目的分析p57kip2和PCNA蛋白在西宁地区食管鳞癌组织中的表达,探讨其在食管鳞癌发生发展中的意义。方法选取60例食管鳞癌及其相对应的31例癌旁正常组织标本,应用免疫组化方法检测p57kip2和PCNA蛋白,并结合临床病理特点分析。结果p57kip2在食管鳞癌中的表达率为28.33%,低于癌旁正常组织的表达率(51.61%),并与食管鳞癌的分化程度、浸润深度有关,差异有统计学意义(P<0.05)。PCNA在食管鳞癌中的表达率为81.67%,高于癌旁正常组织的表达率(61.29%),与食管鳞癌的分化程度、浸润深度、淋巴结转移有关,差异有统计学意义(P<0.05)。p57KIP2与PCNA蛋白的表达呈负相关(rs=-0.611,P<0.01)。结论食管鳞癌组织中p57kip2低表达与PCNA的高表达共同参与食管癌的发生、发展。联合检测可作为预测食管鳞癌恶性程度和预后的重要指标。     

产前诊断47, XN, -18, +inv(18)(p11q21.1), +inv(18)(p11q21.1)一例

报告1例采用传统的染色体核型分析技术对血清学筛查18-三体高风险,超声提示胎儿生长受限（fetal growth restriction,FGR）、室间隔缺损、唇裂合并腭裂、右侧脉络丛囊肿的胎儿进行家系遗传学病因检测,明确了胎儿同时携带1条正常18号染色体及2条18号染色体臂间倒位的衍生染色体。父母染色体核型分析提示2条18号衍生染色体应遗传自母亲。本研究丰富了18-三体综合征的染色体核型变异类型,为今后产前诊断临床咨询提供参考数据。     

Polychlorobiphenyl (PCB) congeners,p,p′-DDE,and hexachlorobenzene in maternal and fetal cord blood from mothers in upstate New York

Whole blood samples were taken from 101 women (26±4 years) entering maternity facilities in upstate New York. At birth, fetal cord blood was also collected. The samples were analyzed for 74 polychlorobiphenyl (PCB) congeners,p,p-DDE, mirex, and hexachlorobenzene by glass capillary gas chromatography with electron capture detection. Maternal blood contained 3.5±1.1 ng total PCB/g whole blood and fetal cord blood contained 2.4±1.0 ng total PCB/g whole blood, which indicate that the women are less contaminated than women surveyed elsewhere in the U.S. Of the 77 compounds measured, only 20 occurred in more than 10% of the maternal samples at levels >0.01 ng/g. Mirex was not detected. Although the concentration of the majority of congeners,p,p-DDE and hexachlorobenzene correlated in maternal and fetal cord blood, 2,5,2,5-tetrachlorobiphenyl and hexachlorobenzene crossed the placenta preferentially. Apparently, the population contains vestiges of Aroclor^® 1242 (the PCB mixture used in electrical equipment) and Aroclor^® 1260 (the mixture used as a plasticizer).p,p- DDE was the pollutant present at highest concentration (maternal 3.8±0.8 ng/g, fetal cord 1.9±0.9 ng/g).