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多氯二苯并对二噁英和二苯并呋喃(polychlorinated dibenzo-p-dioxins and dibenzofurans,PCDD/Fs),也称为二噁英,是持久性有机污染物,已被定性为内分泌干扰物(endocrine-disrupting chemicals,EDCs)。研究发现,EDCs暴露会干扰类固醇激素的生物合成、转运和代谢[1]。二噁英是燃烧过程的副产物[2],在1962—1971年越南战争期间,美军在越南南部喷洒了大量含有二噁英的除草剂,虽然战争已经过去了40多年,但是喷洒区域环境和人体(母乳和血液)中的二噁英含量仍然显著高于非喷洒地区[3-7],特别是在战争期间用于储存除草剂的美国前空军基地周围,被称为二噁英暴露“热点地区”[8]。二噁英暴露可引起皮肤病、肝损伤和不良生殖影响、癌症和神经发育障碍[9-11]。最近的研究结果表明,二噁英暴露会导致成年男性性激素随着年龄的增长而增高,从而导致其罹患前列腺癌症的风险升高[12]。
由于二噁英的亲脂性,使得其能够通过食物摄入在人体脂质中广泛分布和积累,二噁英不仅在人体组织和血浆中积累,而且还可以通过脐带和母乳从母体转移到胎儿[13-15]。流行病学研究表明,围产期暴露于双酚A、二噁英和多氯联苯(polychlorinated biphenyls,PCBs)可能会改变婴幼儿正常的性类固醇激素含量,影响其生殖能力[16-20]。
我们在前期的研究中发现,二噁英暴露地区初产妇母乳中二噁英含量比非暴露区域高约4倍,围产期二噁英暴露导致1岁儿童类固醇激素脱氢表雄酮(dehydroepiandrosterone,DHEA)水平升高[21]。但没有队列研究阐明围产期二噁英暴露对这些儿童类固醇激素的长期影响。本研究通过队列研究揭示围产期二噁英暴露对儿童类固醇激素的长期影响。
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暴露地区为位于越南南部Dong Nai省的Bien Hoa地区(前美国空军基地),在1962—1971年期间污染最严重的除草剂橙剂,约50%储存在Bien Hoa空军基地[22]。非暴露地区位于越南北部Ha Nam省的Kim Bang地区,该地区在战争期间没有喷洒化学除草剂,且附近没有工业污染[23]。于2010年和2011年,在Bien Hoa地区和Kim Bang地区各有37和44对母婴被纳入本次调查研究。被试为20—30岁的初产妇,当孕妇在这两个地区医院分娩时,妇产科医生根据以下标准筛选被试: (1)怀孕期间住在目标地区;(2)出生婴儿为足月儿;(3)孕妇和婴儿出生时均无并发症。
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调查时间分别为儿童1岁(Bien Hoa:2010年8月;Kim Bang:2011年8月),3岁(Bien Hoa:2012年8月;Kim Bang:2013年8月)和5岁时(Bien Hoa:2014年8月;Kim Bang:2015年8月)。测量儿童体重、身高、头围和胸围,并采集唾液样本约1—2 mL,用于分析儿童1岁、3岁和5岁时脱氢表雄酮、睾酮和皮质醇水平。母亲产后4周在助产士或医务人员的协助下采集20 mL母乳样品,用于测量17种二噁英同系物的水平。所有母亲均签署书面知情同意书。本研究通过了日本金泽大学伦理委员会审查(编号:2010-452)。
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在多层硅胶柱和活性炭分散硅胶柱上进行碱消化和色谱纯化操作,分离和收集PCDD/DFs。使用配备有以选定离子监测模式操作的高分辨率质谱仪(气相色谱高分辨率质谱仪;型号:MS—JMS700, JEOL, 东京, 日本电子株式会社)的气相色谱仪(型号:HP—6980,加利福尼亚,美国Hewlett Packaed公司)进行定量。具体分析方法详见参考文献[22]。PCDD/DFs-TEQ的计算参考世界卫生组织2005年毒性当量因子[24]。产后4周母乳中二噁英的含量被认定为婴儿围产期二噁英暴露量[16-20]。
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将含皮质醇-d4(1 ng),DHEA-13C3(200 pg)和睾酮-13C3(400 pg)的80 %乙醇2。5 mL作为内标加入含有唾液的玻璃管内,摇动3—5 min,离心分离溶液,然后用2 mL乙醇进行1次提取。用离心蒸发器在40℃下蒸发混合溶液,100 μL甲醇溶解干燥样品,用1 mL水稀释,4 mL甲基叔丁基甲醚萃取类固醇部分。
纯化后的样品用70 μL无水吡啶酸试剂和20 μL三乙酰胺作为催化试剂。反应30 min后,用1 mL有机混合物溶液(己烷-乙酸乙酯-乙酸∶35∶15∶1)稀释,在硅胶柱上样(柱间硅胶柱:GL Science Ltd,东京)后用5 mL己烷洗涤。用1 mL己烷、1 mL乙酸己烷和类固醇衍生物洗脱,用2 mL丙酮-己烷(7∶3)洗脱。将吡啶甲酸衍生物样品用100 μL 40 %乙腈-水溶解并用于液相色谱-串联质谱。详细分析方法见参考文献[21]。由于1岁儿童唾液中睾酮含量过低无法检测,因此睾酮的含量测定从3岁开始。
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使用JMP-9软件包(SAS institute,Cary,NC,Japan)进行统计分析。采用Student t检验或Mann-Whitney检验,比较二噁英暴露地区和非暴露地区的组间差异。在调整儿童体质指数、胸围和头围后,使用多元线性回归模型分析2组人群中二噁英暴露浓度与类固醇激素之间的相关性。
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不同地区受试人群体征比较见(表1)。 暴露地区男童在各年龄段的身高、体重、体质指数、头围和胸围的生长变量均显著高于非暴露地区。女童1岁时各指标在2个地区间没有显著差异,在3岁和5岁时除3岁儿童体质指数外其他指标暴露地区均高于非暴露地区。暴露地区初产妇的平均年龄为28岁,年龄区间为24—29岁;非暴露地区初产妇的平均年龄为26岁,年龄区间为24—28岁;两者之间没有显著差异(P = 0.083)。暴露地区初产妇在该地区的平均居住年限为27年,居住年限区间为23—28年;非暴露地区初产妇在该地区的平均居住年限为25年,居住年限区间为23—27年,两者之间没有显著差异(P = 0.275)。在本研究中,暴露地区儿童的生长变量显著高于非暴露地区(表1)。前人的研究发现,二噁英暴露对不同年龄段儿童生长发育的影响结果不同[11,25-26]。在较大的年龄段,二噁英暴露使男性受试者生长指数出现减少的趋势而女性受试者增长指数出现增加趋势[11,25-26]。这与本研究中关于女童的生长变量变化趋势一致,然而与男童的生长变量变化趋势相反。由于本项研究受试者人数与上述研究相比相对较少,且随访期间为青春期前,因此该发现需要在今后的研究中进一步验证。
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暴露地区母乳中17种二噁英同系物含量除1,2,3,7,8-PeCDF、1,2,3,7,8,9-HxCDF、2,3,4,6,7,8-HxCDF和OCDF外,其余14种二噁英同系物平均含量显著高于非暴露地区(表2)。
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在男童和女童中,暴露地区DHEA含量在儿童1岁时显著高于非暴露地区,5岁时DHEA含量显著低于非暴露地区,3岁时DHEA含量在两地区之间没有显著差异。男童在5岁时暴露地区的睾酮水平显著低于非暴露地区,女童3岁和5岁时,暴露地区睾酮含量显著低于非暴露地区(表3)。不同年龄段男女儿童皮质醇水平无显著差异。在调整儿童体质指数、胸围和头围后,使用多因素回归模型分析2组人群中二噁英暴露浓度与类固醇激素之间的相关性。结果发现,暴露地区17种同系物中2,3,7,8-TeCDD(β = 0.4235;P = 0.0395)、 1,2,3,7,8-PeCDD(β = 0.4742;P = 0.0190)、1,2,3,4,7,8- HxCDD(β = 0.4949;P = 0.0140)和1,2,3,6,7,8-HxCDD(β = 0.4745;P = 0.0327)以及TEQ PCDD(β = 6566;P = 0.0005)和TEQ PCDD/DF(β = 0.6137;P = 0.0014)与1岁男童DHEA含量呈显著性正相关。在男童5岁时DHEA含量与1,2,3,7,8-PeCDD (β = −0.5925;P = 0.0057)、1,2,3,6,7,8- HxCDD(β = −0.6350;P = 0.0026)和1,2,3,7,8,9-HxCDD(β = −0.5623;P = 0.0108)呈显著性负相关。在男童3岁时,其DHEA和睾酮含量与二噁英同系物之间无相关性。在儿童5岁时睾酮与二噁英之间无相关性。非暴露地区17种二噁英同系物与男童类固醇激素之间无相关性。暴露地区17种同系物中,OCDD与1岁女童DHEA含量呈显著性负相关(β = −0.5987;P = 0.0323)。在女童3岁和5岁时DHEA和睾酮与二噁英之间无相关性。 DHEA作为雄性激素的底物,可以传化为睾酮或双氢睾酮从而获得雄激素活性。DHEA在儿童体内的异常变化可能导致睾酮水平变化异常从而影响儿童早期生殖发育。Miyashitadori等研究发现,男性婴儿脐带血中的脱氢表雄酮水平与母体血液中的二噁英浓度呈显著性正相关,而在女性婴儿中呈显著性负相关[27],与本研究结果一致。已有研究证实,妊娠期二噁英暴露会导致婴幼儿出生后类固醇激素水平出现性别差异[28]。而二噁英对DHEA的影响机制尚未明确。
CYP17作为细胞色素P450C7a酶的编码基因,其表达量的变化会导致P450C7a酶即CYP17A1酶(17a-羟化酶/17-20裂解酶)的活性变化从而导致类固醇激素分泌异常研究表明,CYP17裂解酶能够将17α-羟基孕烯醇酮转化为DHEA[29]。最新的研究发现,二噁英暴露地区学龄前儿童的血清中CYP17裂解酶活性明显高于非暴露地区的儿童,表明二噁英刺激了CYP17裂解酶活性[30]。因此, DHEA水平的升高是二噁英刺激CYP17裂解酶活性的结果,二噁英对男童和女童体内CYP17裂解酶活性调节作用的不同导致了二噁英对DHEA的影响出现了性别差异。二噁英暴露对CYP17裂解酶活性的影响机制仍不清楚。有研究表明,细胞色素b5在CYP17裂解酶活性的调节中起作用[31]。二噁英可能影响细胞色素b5的变构调节功能,导致CYP17裂解酶活性改变[32]。DHEA水平在出生后到1岁之间会持续下降,在1—5岁之间保持一个平稳且较低的水平,6岁时出现上升趋势[29]。在本研究中发现,暴露地区男童和女童在1和5岁时DHEA与二噁英之间存在相关性,而3岁时无相关性,这可能是因为在1岁时是DHEA持续下降到平稳的节点,5岁时是DHAE从平稳且较低的水平到上升的节点。而3岁时处于DHEA保持平稳且较低水平(1—5岁)的中间时间点,是DHEA水平最平稳的时期,因此可能不容易受到外界物质的干扰。皮质醇和DHEA作为肾上腺激素,在人类中受肾上腺皮质激素(ACTH)调节[33-34]。如果二噁英作用于垂体或下丘脑,DHEA和皮质醇在儿童中可能同时改变。而研究只观察到儿童DHEA的变化,因此二噁英可能直接作用于肾上腺皮质的类固醇生物合成途径,而不是作用于通过垂体的ACTH分泌。
由于青春期前儿童的性器官尚未发育,大多数睾丸激素是由肾上腺产生的。这项研究结果,支持我们的假设,即二噁英会干扰青春期前儿童的肾上腺功能。Karman等[35]研究发现,二噁英同类物2,3,7,8-TeCDD暴露导致窦卵泡的睾酮激素水平以及17β-HSD转录及其蛋白质水平的显著降低。Oanh等[30]研究发现,二噁英与5岁儿童的17β-羟类固醇脱氢酶(17β-HSD)酶活性之间呈显著负相关,指出二噁英暴露可能对17β-HSD活性有抑制作用,从而导致睾酮激素水平降低。然而,本研究在使用多元线性回归来调整儿童体质指数、胸围和头围后,发现在3岁和5岁儿童中,睾酮与二噁英同系物无相关性。而近期的研究发现,母乳中的二噁英浓度与婴儿脐带血中的睾酮水平呈显著性负相关[16]。在我们之前研究中同样发现,5岁儿童血清中的睾酮水平与二噁英浓度呈显著性负相关[36]。众所周知,脂肪组织内芳香化酶可将睾酮转化为雌激素,由于本项研究中暴露地区儿童的身体发育状况要好于非暴露地区,其对睾酮的影响可能要强于二噁英暴露的影响,另外本研究的受试者人数相对较少。因此该发现需在今后的研究中进一步验证。
本研究中调整了儿童的体质指数、胸围和头围后,分析了不同地区儿童唾液类固醇激素与二噁英的相关性。但本研究未获得有关父母体征和母乳喂养等营养方面以及类固醇药品使用等方面的相关信息。因此,今后的研究需要在增加上述信息的基础上,进一步分析儿童唾液类固醇激素与二噁英的相关性。
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本研究发现,暴露地区男童1岁时唾液中脱氢表雄酮(DHEA)含量与二噁英同系物中2,3,7,8-TeCDD、 1,2,3,7,8-PeCDD、1,2,3,4,7,8- HxCDD 和1,2,3,6,7,8-HxCDD以及TEQ PCDD和TEQ PCDD/DF呈正相关,5岁时与二噁英同系物1,2,3,7,8-PeCDD 、1,2,3,6,7,8- HxCDD 和1,2,3,7,8,9-HxCDD呈负相关,而女童1岁时与二噁英呈负相关。综上所述,围产期二噁英暴露对儿童早期DHEA含量影响具有性别差异。但是由于本研究的受试者人数相对较少,且追踪年限较短,因此在今后的研究中需要增加受试者人数,并延长追踪调查年限去验证本研究的发现。另外需要增加动物实验,在机制方面去验证二噁英对类固醇激素的影响。
二噁英暴露对儿童早期类固醇激素的影响
Effects of dioxin exposure on steroid hormones in early childhood
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摘要: 为了阐明在儿童重要发育阶段二噁英对其内分泌的干扰。本研究于2010年和2011年,招募二噁英暴露地区37对母婴和非暴露地区44对母婴,运用气相色谱-质谱法测定母乳中二噁英含量,运用液相色谱-串联质谱法测定儿童唾液类固醇激素含量。结果显示,暴露地区母乳中二噁英含量(Mean=11.0 pg·lipid−1)明显高于非暴露地区(Mean=3.4 pg·lipid−1)。暴露地区男童1岁时唾液中脱氢表雄酮(DHEA)含量与二噁英同系物中2,3,7,8-TeCDD(β=0.4235;P=0.0395)、 1,2,3,7,8-PeCDD(β=0.4742;P=0.0190)、1,2,3,4,7,8- HxCDD(β=0.4949;P=0.0140)和1,2,3,6,7,8-HxCDD(β=0.4745;P=0.0327)以及TEQ PCDD(β=0.6566;P=0.0005)和TEQ PCDD/DF(β=0.6137;P=0.0014)呈正相关(P<0.05),5岁时与二噁英同系物1,2,3,7,8-PeCDD(β=−0.5925;P=0.0057)、1,2,3,6,7,8- HxCDD(β=−0.6350;P=0.0026)和1,2,3,7,8,9-HxCDD(β=−0.5623;P=0.0108)呈负相关(P<0.05),而女童1岁时与二噁英呈负相关(P<0.05),但5岁时无相关性(P>0.05)。综上所述,围产期二噁英暴露对儿童早期DHEA含量影响具有性别差异。Abstract: The present study was to follow up and more clearly elucidate this endocrine disruption by dioxin during the important developmental stages of children.In 2010 and 2011, 37 mother–infant pairs in the exposed region and 44 pairs in the non-exposed region were enrolled in the present study.Dioxin was determined by gas chromatography-mass spectrometry. Saliva steroid hormones were determined by liquid chromatography-tandem mass spectrometry. The results showed that breast milk levels of dioxin congeners in the exposed region (Mean=11.0 pg·lipid−1) were significantly higher than the non-exposed region (Mean=3.4 pg·lipid−1). In the exposed region, dehydroepiandrosterone (DHEA) in saliva of boys was positively correlated with 2,3,7,8-TeCDD (β=0.4235; P=0.0395), 1,2,3,7,8-PeCDD (β=0.4742; P=0.0190), 1,2,3,4,7,8- HxCDD (β=0.4949; P=0.0140), 1,2,3,6,7,8-HxCDD (β=0.4745; P=0.0327), TEQ PCDD (β=6566; P=0.0005), and TEQ PCDD/DF(β=0.6137; P=0.0014) at the age of 1 (P < 0.05) and negatively correlated with 1,2,3,7,8-PeCDD (β=−0.5925; P=0.0057), 1,2,3,6,7,8- HxCDD (β=−0.6350; P=0.0026), and 1,2,3,7,8,9-HxCDD (β=−0.5623; P=0.0108) at the age of 5 (P<0.05).An increase in maternal dioxins related to increased DHEA levels in male salivary samples. However, an increase dioxin related to decreased DHEA levels in female salivary samples at the age of 1 (P<0.05), but not at the age of 5 (P>0.05). Our founding suggested that the effect of perinatal dioxin exposure on children's early DHEA content has gender differences.
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Key words:
- dioxin /
- children /
- steroid hormones /
- cohort study
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表 1 不同地区儿童生长指标测量结果比较
Table 1. Demographic characteristics of participants
指标 男童 Boy 女童 Girl 暴露地区
Exposed
(n=25)非暴露地区
Non-exposed
(n=22)F P 暴露地区
Exposed
(n=12)非暴露地区
Non-exposed
(n=22)F P 1岁儿童 身高/m 0.63±0.04 0.59±0.04 11.72 0.001 0.59±0.05 0.57±0.05 2.17 0.151 体重 /kg 6.5±1.3 5.2±1.1 14.62 0.000 5.4±1.1 4.6±1.0 4.17 0.049 体质指数/(kg·m−2) 16.1±1.6 14.8±1.4 10.40 0.002 15.4±1.5 14.4±1.7 3.18 0.084 头围 /cm 40.0±1.9 38.6±1.6 6.99 0.011 38.3±1.8 37.6±1.7 1.38 0.249 胸围 /cm 41.7±3.1 38.9±3.1 10.86 0.002 39.0±2.6 37.4±3.1 2.19 0.149 3 岁儿童 身高/m 0.99±0.03 0.93±0.05 18.16 0.000 0.96±0.03 0.90±0.03 22.28 0.000 体重/kg 16.9±3.2 13.5±1.3 23.05 0.000 14.5±1.2 12.4±1.4 16.74 0.000 体质指数/(kg·m−2) 17.2±2.3 15.5±1.1 11.03 0.005 15.7±0.8 15.3±1.2 1.13 0.296 头围/cm 50.2±1.4 48.5±1.3 16.93 0.000 48.8±1.5 47.4±1.0 9.56 0.004 胸围/cm 55.7±4.3 50.2±2.5 27.48 0.000 51.7±1.5 49.0±1.8 18.07 0.000 5 岁儿童 身高/m 1.14±0.04 1.09±0.06 7.57 0.009 1.11±0.09 1.05±0.08 29.38 0.000 体重 /kg 23.0±4.7 17.8±2.5 21.78 0.000 20.2±2.2 14.8±2.5 33.44 0.000 体质指数/(kg·m−2) 17.7±2.9 14.9±1.4 18.62 0.000 15.7±1.6 14.5±1.2 5.75 0.023 头围/cm 51.5±1.3 50.2±1.1 14.35 0.001 50.9±1.5 49.6±1.0 7.89 0.009 胸围/cm 59.5±7.3 54.3±3.8 23.73 0.000 56.8±3.3 52.2±2.3 22.76 0.000 表 2 不同地区母乳中二噁英含量比较
Table 2. comparison of dioxins levels in breast milk between exposed and non-exposed regions
化合物 暴露地区/pg(lipid)
Exposed
(n = 37)非暴露地区/pg(lipid)
Non-exposed
(n = 44)P F M P25—P75 M P25—P75 2,3,7,8-TeCDD 2.0 1.0—3.6 0.5 0.4—0.9 13.87 <0.0001 1,2,3,7,8-PeCDD 2.8 2.0—4.2 1.1 0.7—1.7 49.85 <0.0001 1,2,3,4,7,8-HxCDD 1.4 1.0—2.0 0.8 0.5—1.4 19.05 <0.0001 1,2,3,6,7,8-HxCDD 5.2 2.8—7.4 1.3 0.9—1.7 51.63 <0.0001 1,2,3,7,8,9-HxCDD 1.5 1.1—2.5 0.5 0.4—0.9 39.80 <0.0001 1,2,3,4,6,7,8-HpCDD 8.3 6.0—14.1 2.6 1.8—3.3 36.04 <0.0001 OCDD 58.4 41.0—78.8 15.7 10.5—15.7 62.99 <0.0001 2,3,7,8-TeCDF 0.5 0.3—0.6 0.7 0.4—0.9 5.30 0.0079 1,2,3,7,8-PeCDF 0.5 0.4— 0.7 0.4 0.2—0.6 1.50 0.1883 2,3,4,7,8-PeCDF 4.1 3.4—5.4 3.1 2.4—3.8 15.08 0.0002 1,2,3,4,7,8-HxCDF 6.3 5.1—10.0 1.6 1.3—2.0 34.79 <0.0001 1,2,3,6,7,8-HxCDF 4.0 2.9—5.7 1.4 1.0—1.5 32.40 <0.0001 1,2,3,7,8,9-HxCDF 0.3 0.2—0.6 0.3 0.2—0.4 1.77 0.5888 2,3,4,6,7,8-HxCDF 0.7 0.4—0.9 0.6 0.3—0.8 4.54 0.1347 1,2,3,4,6,7,8-HpCDF 4.6 3.1— 5.6 1.1 0.8—1.5 24.76 <0.0001 1,2,3,4,7,8,9-HpCDF 0.7 0.3—1.1 0.2 0.2—0.3 24.78 <0.0001 OCDF 0.6 0.5—1.0 0.6 0.5—0.8 0.02 0.8783 TEQ Total PCDDs 8.1 5.7—11.3 2.3 1.6—3.5 67.99 <0.0001 Total PCDFs 2.4 1.7—3.1 1.1 0.9—1.2 29.38 <0.0001 Total PCDDs + PCDFs 11.0 7.5—15.1 3.4 2.5—4.3 74.40 <0.0001 表 3 不同地区儿童唾液类固醇激素比较
Table 3. Comparison of saliva steroid hormone levels between exposed and non-exposed region
男孩 Boy 女孩 Girl 暴露地区
Exposed
(n=25)非暴露地区
Non-exposed
(n=22)P 暴露地区
Exposed
(n=12)非暴露地区
Non-exposed
(n=22)P M P25—P75 M P25—P75 M P25—P75 M P25—P75 1岁儿童 可的松/ (pg·mL−1) 757 597—1261 766 623—1146 0.9150 1065 760—1530 860 562—1264 0.36760 DHEA/(pg·mL−1) 105 79—105 25 17—46 <0.0001 124 75—168 32 23—53 <0.0001 3 岁儿童 可的松/ (pg·mL−1) 550 309—972 857 475—1134 0.1012 541 226—1210 449 295—749 0.9533 DHEA/ (pg·mL−1) 156 92—262 189 78—439 0.5671 206 76—440 208 154—323 0.9117 睾酮/ (pg·mL−1) 2.0 1.1—3.4 2.8 2.0—4.7 0.0848 2.3 2.0—6.6 3.1 1.6—4.5 0.0021 5 岁儿童 可的松/ (pg·mL−1) 829 440—1202 522 372—824 0.1807 714 85—1165 756 339—1066 0.4319 DHEA /(pg·mL−1) 79 40—140 339 273—761 <0.0001 97 61—178 675 320—924 <0.0001 睾酮/ (pg·mL−1) 1.0 1.0—2.0 4.5 2.7—7.9 <0.0001 1.2 1.0—1.7 7.0 3.2—13.2 <0.0001 -
[1] 陈玫宏, 郭敏, 刘丹, 等. 典型内分泌干扰物在太湖及其支流水体和沉积物中的污染特征 [J]. 中国环境科学, 2017, 37(11): 4323-4332. doi: 10.3969/j.issn.1000-6923.2017.11.038 CHEN M H, GUO M, LIU D, et al. Occurrence and distribution of typical endocrine disruptors in surface water and sediments from Taihu Lake and its tributaries [J]. China Environmental Science, 2017, 37(11): 4323-4332(in Chinese). doi: 10.3969/j.issn.1000-6923.2017.11.038
[2] 刘帅, 张震, 宋国君, 等. 北京某垃圾焚烧厂二噁英多介质扩散风险评估 [J]. 中国公共卫生, 2018, 34(9): 1224-1228. doi: 10.11847/zgggws1117325 LIU S, ZHANG Z, SONG G J, et al. Health risk assessment on dioxin emission from a waste incineration plant in Beijing city based on multi-medium diffusion model [J]. Chinese Journal of Public Health, 2018, 34(9): 1224-1228(in Chinese). doi: 10.11847/zgggws1117325
[3] 罗挺, 陈敏慧, 罗云程, 等. 二噁英暴露与6种疾病流行: 越南成年男性的健康研究 [J]. 环境化学, 2019, 38(8): 1669-1675. doi: 10.7524/j.issn.0254-6108.2018093003 LUO T, CHEN M H, LUO Y C, et al. Dioxin exposure and six kind of diseases prevalence: Vietnamese men health study [J]. Environmental Chemistry, 2019, 38(8): 1669-1675(in Chinese). doi: 10.7524/j.issn.0254-6108.2018093003
[4] MANH HD, KDIO T, OKAMOTO R, et al. Serum dioxin levels in Vietnamese men more than 40 years after herbicide spraying [J]. Environmental Science & Technology, 2014, 48(6): 3496-3503. [5] MANH H D, KIDO T, TAI P T, et al. Levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans in breast milk samples from three dioxin-contaminated hotspots of Vietnam [J]. Science of The Total Environment, 2015, 511: 416-422. doi: 10.1016/j.scitotenv.2014.12.083 [6] NGHI T N, NISHIJO M, MANH H D, et al. Dioxins and nonortho PCBs in breast milk of Vietnamese mothers living in the largest hot spot of dioxin contamination [J]. Environmental Science & Technology, 2015, 49(9): 5732-5742. [7] SCHECTER A, DAI LC, THUY L, et al. Agent orange and the Vietnamese: The persistence of elevated dioxin levels in human tissues [J]. American Journal of Public Health, 1995, 85(4): 516-522. doi: 10.2105/AJPH.85.4.516 [8] DWERNYCHUK LW. Dioxin hot spots in Vietnam [J]. Chemosphere, 2005, 60(7): 998-999. doi: 10.1016/j.chemosphere.2005.01.052 [9] Institute of medicine, 2009. Veterans and Agent Orange: update 2008. Washington, DC: National Academy Press 2009[EB/R]. [2009-12-2].https://www.nap.edu/catalog/12662/veterans-and-agent-orange-update-2008. [10] NISHIJO M, PHAM T T, NGUYEN A T N, et al. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam [J]. Molecular Psychiatry, 2014, 19(11): 1220-1226. doi: 10.1038/mp.2014.18 [11] TAI P T, NISHIJO M, NGHI T N, et al. Effects of perinatal dioxin exposure on development of children during the first 3 years of life [J]. The Journal of Pediatrics, 2016, 175: 159-166.e2. doi: 10.1016/j.jpeds.2016.04.064 [12] SUN XL, KIDO T, HONMA S, et al. The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men [J]. Science of The Total Environment, 2017, 595: 842-848. doi: 10.1016/j.scitotenv.2017.04.013 [13] SCHECTER A, PAPKE O, BALL M. Evidence for transplacental transfer of dioxins from mother to fetus: Chlorinated dioxin and dibenzofuran levels in the livers of stillborn infants [J]. Chemosphere, 1990, 21(8): 1017-1022. doi: 10.1016/0045-6535(90)90124-C [14] SUZUKI G, NAKANO M, NAKANO S. Distribution of PCDDs/PCDFs and co-PCBs in human maternal blood, cord blood, placenta, milk, and adipose tissue: Dioxins showing high toxic equivalency factor accumulate in the placenta [J]. Bioscience, Biotechnology, and Biochemistry, 2005, 69(10): 1836-1847. doi: 10.1271/bbb.69.1836 [15] WANG S L, LIN C, GUO Y L, et al. Infant exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls (PCDD/Fs, PCBs): Correlation between prenatal and postnatal exposure [J]. Chemosphere, 2004, 54(10): 1459-1473. doi: 10.1016/j.chemosphere.2003.08.012 [16] BODA H, NGHI T N, NISHIJO M, et al. Prenatal dioxin exposure estimated from dioxins in breast milk and sex hormone levels in umbilical cord blood in Vietnamese newborn infants [J]. The Science of the Total Environment, 2018, 615: 1312-1318. doi: 10.1016/j.scitotenv.2017.09.214 [17] CAO Y G, WINNEKE G, WILHELM M, et al. Environmental exposure to dioxins and polychlorinated biphenyls reduce levels of gonadal hormones in newborns: Results from the Duisburg cohort study [J]. International Journal of Hygiene and Environmental Health, 2008, 211(1/2): 30-39. [18] GOUDARZI H, ARAKI A, ITOH S, et al. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: The Hokkaido study [J]. Environmental Health Perspectives, 2017, 125(1): 111-118. doi: 10.1289/EHP142 [19] RENNERT A, WITTSIEPE J, KASPER-SONNENBERG M, et al. Prenatal and early life exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls may influence dehydroepiandrosterone sulfate levels at prepubertal age: Results from the Duisburg birth cohort study [J]. Journal of Toxicology and Environmental Health, Part A, 2012, 75(19/20): 1232-1240. [20] SATHYANARAYANA S, BUTTS S, WANG C, et al. Early prenatal phthalate exposure, sex steroid hormones, and birth outcomes [J]. The Journal of Clinical Endocrinology & Metabolism, 2017, 102(6): 1870-1878. [21] ANH L T, KIDO T, HONMA S, et al. A relationship in adrenal androgen levels between mothers and their children from a dioxin-exposed region in Vietnam [J]. The Science of the Total Environment, 2017, 607/608: 32-41. doi: 10.1016/j.scitotenv.2017.06.264 [22] DWERNYCHUK L W, CAU H D, HATFIELD C T, et al. Dioxin reservoirs in southern vietnam-A legacy of agent orange [J]. Chemosphere, 2002, 47(2): 117-137. doi: 10.1016/S0045-6535(01)00300-9 [23] MANH H D, KIDO T, OKAMOTO R, et al. The relationship between dioxins and salivary steroid hormones in Vietnamese primiparae [J]. Environmental Health and Preventive Medicine, 2013, 18(3): 221-229. doi: 10.1007/s12199-012-0310-x [24] van den BERG M, BIRNBAUM L S, DENISON M, et al. The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds [J]. Toxicological Sciences, 2006, 93(2): 223-241. doi: 10.1093/toxsci/kfl055 [25] ISZATT N, STIGUM H, GOVARTS E, et al. Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years: A pooled analysis of three European birth cohorts [J]. Environment International, 2016, 94: 399-407. doi: 10.1016/j.envint.2016.04.040 [26] WANG Z, HANG J G, FENG H, et al. Effects of perinatal dioxin exposure on development of children: A 3-year follow-up study of China cohort [J]. Environmental Science and Pollution Research, 2019, 26(20): 20780-20786. doi: 10.1007/s11356-019-05362-0 [27] MIYASHITA C, ARAKI A, MITSUI T, et al. Sex-related differences in the associations between maternal dioxin-like compounds and reproductive and steroid hormones in cord blood: The Hokkaido Study [J]. Environment International, 2018, 117: 175-185. doi: 10.1016/j.envint.2018.04.046 [28] LI L A, WANG P W. PCB126 induces differential changes in androgen, cortisol, and aldosterone biosynthesis in human adrenocortical H295R cells [J]. Toxicological Sciences, 2005, 85(1): 530-540. doi: 10.1093/toxsci/kfi105 [29] MILLER W L, AUCHUS R J. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders [J]. Endocrine Reviews, 2011, 32(1): 81-151. doi: 10.1210/er.2010-0013 [30] OANH NTP, KIDO T, HONMA S, et al. Androgen disruption by dioxin exposure in 5-year-old Vietnamese children: Decrease in serum testosterone level [J]. Science of The Total Environment, 2018, 640-641: 466-474. doi: 10.1016/j.scitotenv.2018.05.257 [31] BHATT M R, KHATRI Y, RODGERS R J, et al. Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17α-hydroxylase/17, 20-lyase (P450 17A1) [J]. The Journal of Steroid Biochemistry and Molecular Biology, 2017, 170: 2-18. doi: 10.1016/j.jsbmb.2016.02.033 [32] KIDO T, HONMA S, NHU D D, et al. Inverse association of highly chlorinated dioxin congeners in maternal breast milk with dehydroepiandrosterone levels in three-year-old Vietnamese children [J]. The Science of the Total Environment, 2016, 550: 248-255. doi: 10.1016/j.scitotenv.2016.01.025 [33] REGE J, NAKAMURA Y, SATOH F, et al. Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein 19-carbon steroids before and after ACTH stimulation [J]. The Journal of Clinical Endocrinology & Metabolism, 2013, 98(3): 1182-1188. [34] STÁRKA L, DUŠKOVÁ M, HILL M. Dehydroepiandrosterone: a neuroactive steroid [J]. The Journal of Steroid Biochemistry and Molecular Biology, 2015, 145: 254-260. doi: 10.1016/j.jsbmb.2014.03.008 [35] KARMAN B N, BASAVARAJAPPA M S, HANNON P, et al. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia [J]. Toxicology and Applied Pharmacology, 2012, 264(1): 1-12. doi: 10.1016/j.taap.2012.07.031 [36] 施丽丽, 董晶剑, 王凤华, 等. 围产期二噁英暴露对学龄前儿童类固醇激素的影响 [J]. 环境科学学报, 2019, 39(8): 2754-2763. SHI L L, DONG J J, WANG F H, et al. Effects of perinatal dioxin exposure on steroid hormones in preschool children [J]. Acta Scientiae Circumstantiae, 2019, 39(8): 2754-2763(in Chinese).
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