Bioturbation effects on cadmium and zinc transfers from a contaminated sediment and on metal bioavailability to benthic bivalves

The two main objectives of this study were to compare cadmium and zinc fluxes from a contaminated sediment to the water column in bioturbated and unbioturbated systems and jointly to analyze accumulation kinetics of these released metals by benthic filter-feeder bivalves. The experimental approach was based on indoor microcosms containing a two-compartment biotope: natural contaminated sediment (45 +/- 5 microg Cd/g, dry wt, and 1,938 +/- 56 microg Zn/g, dry wt) and water column. Four experimental conditions were studied: no organism added to the sediment-water biotope, presence of bivalves Corbicula fluminea, presence of Hexagenia rigida nymphs (bioturbation source), and presence of C. fluminea and H. rigida simultaneously. Results reveal that bioturbation produces a significant metal release into the water column via the resuspended sediment particles. The use of C. fluminea as an indicator of transferred metals in the water column shows that the metal bioavailability is very limited, quantities of cadmium and zinc bioaccumulated in the soft bodies being less than those measured in unbioturbated systems. This experimental study demonstrates that only the dissolved fraction resulting from diffusive metal fluxes across the sediment-water interface is bioavailable for this bivalve species.     

镉对大鼠胰脏的毒作用

目的探讨镉对内分泌和外分泌功能的影响。方法将96只SD大鼠分为4组,分别为对照组和50、100、200mg/LCdCl2染毒组,饮水染毒30、60、90d。测定不同染毒时间大鼠血糖、尿糖、血胰岛素、淀粉酶的改变及血液中金属含量的改变;测定尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG);并测定了胰脏组织中金属的含量以及胰脏金属硫蛋白基因、胰岛素基因和淀粉酶基因的表达情况。结果染毒组大鼠血糖水平在染毒90d的中、高剂量组有明显增加,差异有统计学意义(P<0.05),中剂量组血糖平均值为5.83mmol/L,高剂量组为6.46mmol/L;发现尿糖水平的增高先于尿NAG的增高。各剂量组大鼠血液和胰脏中镉的含量明显增加。在染毒90d中、高剂量组血锌含量降低。在染毒30d的中、高剂量组血液中胰岛素水平明显降低,而血淀粉酶改变不明显。在染毒90d的中、高剂量组胰脏组织中锌的含量明显增加。胰脏中金属硫蛋白基因表达均有不同程度的增加;胰岛素基因的表达除染毒60d中剂量组明显降低外,其他各组差异均无统计学意义(P>0.05)。而胰淀粉酶的基因表达在染毒60d和90d的中、高剂量组均明显增高。结论镉可以在胰脏组织蓄积,引起组织中必需元素锌水平的改变,导致基因和蛋白表达的改变,进一步引起胰脏内、外分泌功能的改变。     

电磁脉冲诱导小鼠肠组织基因表达谱的变化

目的用基因芯片技术研究电磁脉冲(EMP)对小鼠肠组织的生物效应。方法将12只小鼠随机分为正常组和EMP组(每组6只),用200kV/m,200次的电磁脉冲辐照大鼠,于照后第18h,活杀小鼠,取空肠,提取RNA,经反转录后用Cy3、Cy5荧光标记,获得两组动物来源cDNA探针;cDNA探针与基因表达谱芯片进行杂交,结果由扫描仪扫描并用软件进行分析统计。结果EMP组与正常组相比,有56条基因表达发生了明显变化,其中有37条基因表达水平明显升高,而19条基因表达量明显下降。在表达异常的基因中有19条基因是已知功能或部分功能的基因,其中α-catenin胞质蛋白、淋巴细胞同型抗原、谷氨酰果糖6磷酸氨基转移酶、核糖体蛋白S17、小富脯氨酸蛋白2A、腺状激肽释放酶、脂氧合酶、醛酮还原酶、RNA结合蛋白、α-胰淀粉酶2、弹性蛋白酶2、p6-5淋巴细胞抑制因子基因等12条为表达上调基因;Jam新连接粘附分子、精氨酸甲基转移酶,Carm1、NNP-1、2-5寡腺苷酸合成酶、Mlark、ATP合成酶α亚基、解偶联蛋白基因等7条为表达下调基因,其余37条则为未知功能的基因。结论电磁脉冲辐照可诱导小鼠肠组织多个基因特异性表达,且上调基因数居多。     

锌缺乏对培养小鼠胚胎长骨骺板c-fos基因转录和表达的影响

采用体外培养方法研究锌缺乏对小鼠胚胎长骨骺板ｃ－ｆｏｓ基因（ｃ－ｆｏｓ）转录与表达的影响。将孕龄１６天的小鼠胚胎长骨体外培养４８小时（培养基为ＧＢＪｂ）,通过免疫组化及原位杂交方法观察培养长骨ｃ－ｆｏｓｌ转录与表达的变化,并用图像分析系统对结果进行分析。根据培养基的锌浓度将实验分为对照组,缺锌组,缺锌补锌组,锌刺激量组。     

Response of the bivalve Unio tumidus and freshwater communities in artificial streams for hazard assessment of methyl methacrylate

In artificial streams (pilot rivers) supplied with the river water of Gave de Pau (France), we studied the effects of methyl methacrylate (MMA) on the autochthonous bivalve Unio tumidus transferred into the streams and on natural freshwater communities colonizing the channels. Unio tumidus and freshwater communities were exposed to MMA for 15 and 30 d, respectively, at measured concentrations ranging from 0.6 to 122 mg/L. Biomarkers studied in the digestive gland and gills of U. tumidus comprised detoxication systems (namely, antioxidant enzyme activities and glutathione status) and lipid peroxidation as a marker of cytotoxicity. Biocoenotic indicators were used to evaluate effects on benthic invertebrates and diatoms. In bivalves, a decrease in antioxidant levels was found at the lowest concentrations tested (0.6 and 6 mg/L), whereas an increase in lipid peroxidation and mortality was registered at 30 mg/L after 15 d of exposure. Disturbances in freshwater communities occurred after 30 d at MMA concentrations of greater than 30 mg/L. Antioxidant responses in bivalves were recorded at the lowest MMA concentration tested, which was close to the predicted no-effect concentration (0.74 mg/L), and cytotoxicity was registered at a concentration corresponding to the 21-d no-observed-effect concentration for Daphnia magna. On the basis of the criteria studied, antioxidant biomarkers of bivalves appeared to be more sensitive than biocoenotic indicators to MMA.     

二羟环氧苯并芘诱发细胞恶变后基因和蛋白表达差异分析

目的研究苯并(a)芘代谢产物反式二羟环氧苯并芘(反式-BPDE)诱发人支气管上皮细胞系(16HBE)恶性转化的基因和蛋白表达的改变,探讨苯并(a)芘致癌的分子机制.方法应用含4096条人类全长基因的cDNA芯片检测反式-BPDE诱发人支气管上皮细胞恶性转化的基因表达谱的变化;应用二维凝胶电泳技术和相应软件ImageMaster2D 3.10分析反式-BPDE诱发人支气管上皮细胞恶性转化的蛋白质组变化,基质辅助激光解吸电离-飞行时间-质谱结合数据库检索鉴定部分表达有差异的蛋白斑点.结果BPDE诱发的恶性转化细胞与阴性对照细胞比较,cDNA芯片结果显示差异表达基因有143条,其中52条基因在BPDE诱发的恶性转化细胞中表达增高,91条基因在恶性转化细胞中表达降低;二维凝胶电泳显示有72个蛋白斑点出现表达差异,其中44个蛋白斑点在BPDE诱发的恶性转化细胞中表达升高,28个蛋白斑点在恶性转化细胞中表达降低,对其中7个表达明显差异的蛋白斑点的鉴定显示,原癌基因v-erbb2同源3、锌指蛋白127、硫氧还原蛋白过氧化物酶2、KIAA0471蛋白在恶性转化细胞中高表达,而钙结合蛋白5、锌指蛋白Aiolos、Kelch样蛋白3在恶性转化细胞中低表达.结论反式-BPDE诱发16HBE恶性转化的基因表达谱和蛋白表达谱发生了显著的变化,这些表达改变的基因和蛋白可能参与了BPDE诱发细胞恶变的过程.     

维生素A和锌营养水平与小鼠胚胎HOX基因表达的相关性

目的 研究不同维生素A、锌营养水平与小鼠胚胎HOX C4（3.5）基因表达的相关关系。方法 昆明种雌鼠随机均分为3组;缺乏组喂饲无维生素A和低锌饲料;补充组：开始时饲料同缺乏组,母鼠受孕第7天改为富含维生素A和锌的饲料;正常组自始至终喂饲正常饲料。动物喂养至出现明显维生素A、锌缺乏症状后进行交配。受孕第12天取出相应数量孕鼠处死,取样测生化指标;取胚胎测定HOX C4(3.5）基因mRNA表达量。结果 缺乏组、补充组和正常组母鼠血清维生素A水平均值分别为0.44umol/L、1.03umol/L和1.40umol/L,股骨锌含量均值分别为124.3mg/kg、152.1mg/kg和193.8mg/kg,差异有显性。胚胎HOX C4（3.5)基因表达也显升高。结论 小鼠机体维生素A和锌营养水平与胎鼠HOX C4(3.5）基因表达呈高度正相关,各项指标相关系数为0.78～0.99。     

Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans

A bioassay for zinc status in humans has been sought due to the importance of zinc, an essential trace metal, for many divergent functions in the human body; however, a sensitive bioassay for zinc status in humans is lacking. To address this issue, we established gene expression profiles of human lymphoblastoid cells treated with 0 or 30 micro mol/L ZnSO(4) using microarray technology. A limited number of genes were responsive to 30 micro mol/L zinc based on the analysis of Affymetrix human genome U133A GeneChips. We also examined the gene expression patterns of zinc transporters in human lymphoblastoid cells using quantitative RT-PCR analysis. ZNT1 was upregulated in lymphoblastoid cells, whereas ZIP1 was downregulated in response to the increased zinc concentrations in the culture media. To evaluate the potential applications of using both zinc transporter genes as biomarkers of zinc status, we measured the expression levels of ZIP1 and ZNT1 in the peripheral leukocytes collected from 2 different age groups of Korean women. After administration of a zinc supplement (22 mg zinc gluconate/d for 27 d), ZIP1 expression decreased by 17% (P < 0.01) and 21% (P < 0.05) in the peripheral leukocytes collected from 15 young (20-25 y) and 10 elderly (64-75 y) subjects, respectively. ZNT1 expression was not affected by taking the zinc supplement. These data suggest a potential application of ZIP1 as a biomarker of zinc status in humans.     

Remobilization and bioavailability of cadmium from historically contaminated sediments: influence of bioturbation by tubificids

The effects of bioturbation by tubificids on cadmium (Cd) remobilization and bioavailability from sediment were studied throughout two experiments. With bioturbation, particulate Cd was transitorily released into the overlying water, in correlation with sediment resuspension (maximum of 6.1+/-0.1 microg L(-1) after 6 days). Cd bioaccumulation by the bivalve Corbicula fluminea was very limited (maximum of 1.73+/-0.34 microg g(-1), dw), and independent of the algae diet. In contrast, without bioturbation, the release of dissolved Cd increased with the duration of the experiments (maximum of 9.9+/-0.8 microg L(-1) after 36 days). Cd bioaccumulation by C. fluminea varied according to their diet: low bioaccumulation when no algae were added (2.18+/-0.29 microg g(-1), dw), higher bioaccumulation when algae were added throughout the experiment (8.52+/-1.61 microg g(-1), dw), and the highest bioaccumulation when algae were added only during the last 10 days of the experiment (19.66+/-4.63 microg g(-1), dw).     

含镉粉尘治理前后工人尿镉与血镉水平分析

目的 分析某锌粉加工厂含镉粉尘治理前后作业工人尿镉、血镉和尿β2-微球蛋白的变化.方法 对锌粉加工厂粉尘进行治理,对粉尘治理前后84名镉作业工人尿镉、血镉、β2-微球蛋白水平进行自身对照分析.结果 治理后,作业场所锌尘几何均数由3.38mg/m3降至2.22mg/m3,差异有统计学意义(P＜0.01).治理前调查对象的血镉、尿镉几何均数浓度[血镉(2.19±1.19)μg/L,尿镉(1.96±0.74)μg/gCr]明显高于治理后1年[(1.63±0.83)μg/L,(1.25±0.83)μg/g Cr]和治理后2年[(1.36±0.95)μg/L,(0.94±0.72)μg/g Cr],差异有统计学意义(P＜0.01).治理前及治理后1年、2年接触工人尿镉与血镉浓度作相关分析,r=0.466,差异有统计学意义(P＜0.01).结论 粉尘治理能降低低浓度镉作业工人的血镉、尿镉水平,对防止镉中毒效果明显.     

Reproductive toxicity of low-level lead exposure in men

Parameters of semen quality, seminal plasma indicators of secretory function of the prostate and seminal vesicles, sex hormones in serum, and biomarkers of lead, cadmium, copper, zinc, and selenium body burden were measured in 240 Croatian men 19-52 years of age. The subjects had no occupational exposure to metals and no known other reasons suspected of influencing male reproductive function or metal metabolism. After adjusting for age, smoking, alcohol, blood cadmium, and serum copper, zinc, and selenium by multiple regression, significant (P<0.05) associations of blood lead (BPb), delta-aminolevulinic acid dehydratase (ALAD), and/or erythrocyte protoporphyrin (EP) with reproductive parameters indicated a lead-related increase in immature sperm concentration, in percentages of pathologic sperm, wide sperm, round sperm, and short sperm, in serum levels of testosterone and estradiol, and a decrease in seminal plasma zinc and in serum prolactin. These reproductive effects were observed at low-level lead exposure (BPb median 49 microg/L, range 11-149 microg/L in the 240 subjects) common for general populations worldwide. The observed significant synergistic effect of BPb and blood cadmium on increasing serum testosterone, and additive effect of a decrease in serum selenium on increasing serum testosterone, may have implications on the initiation and development of prostate cancer because testosterone augments the progress of prostate cancer in its early stages.     

Inorganic mercury detection by valve closure response in the freshwater clam Corbicula fluminea: integration of time and water metal concentration changes

The objective of the present study was to monitor water-quality assessment by a biological method. Optimum dissolved inorganic mercury sensitivity in the freshwater bivalve Corbicula fluminea was estimated using a combined approach to determine their potentials and limits in detecting contaminants. Detection by bivalves is based on shell closure, a protective strategy when exposed to a water contaminant. To take the rate of spontaneous closures into account, stress associated with fixation by one valve in common valvometers was integrated, and the spontaneous rhythm was associated with daily activity. The response in conditions where the probability of spontaneous closing is the lowest was thus taken into account. To develop dose-response curves, impedance valvometry, in which lightweight impedance electrodes are applied to study free-ranging animals in low-stress conditions, also was used combined with a new analytical approach. The logistic regression dose-response curves take into account variations in both response time and metal concentration in water to significantly improve the methods aiming at determining the optimal sensitivity threshold response. This approach demonstrates that in C. fluminea, inorganic mercury concentrations under the range of 2.0 to 5.1 microg/L (95% confidence interval) cannot be detected within 5 h of addition.     

镉对HepG2细胞DNA损伤作用以及对gadd基因表达的影响

目的 探讨氯化镉对HepG2细胞DNA损伤作用以及对gadd153和gadd45β启动子和mRNA表达的影响.方法 应用彗星试验检测氯化镉对HepG2细胞的DNA损伤作用;分别构建含有gadd153和gadd45β启动子和荧光素酶报告基因的载体pGADD153-Luc和pG45-Luc,荧光素酶活性检测反映gadd153和gadd45β启动子的活性,生物发光检测荧光素酶活性;反转录-聚合酶链反应(RT-PCR)检测gadd153和gadd45β基因mRNA的表达.结果 彗星试验结果显示,在100、300 μmol/L氯化镉处理细胞24 h后,Olive尾矩(分别为0.78±0.06、1.10±0.12)明显高于对照组(0.53±0.08),差异有统计学意义(P<0.05),并有良好的剂量-效应关系(r=0.9761,P<0.05);报告基因分析显示,1、5、10 μmol/L氯化镉处理组gadd153启动子表达[分别为(9.45±1.26)、(11.76±1.12)、(21.14±1.47)RIU/μg Pro]均明显高于对照组[(7.02±0.82)RIU/μg Pro]差异均有统计学意义(P<0.05),并有良好的剂量-效应关系(r=0.8755,P<0.05);5、10μmol/L氯化镉处理组gadd45β启动子表达明显高于对照组,差异有统计学意义(P<0.05),并有良好的剂量-效应关系(r=0.8856,P<0.05);RT-PCR结果显示,1、5、10μmol/L氯化镉处理组gadd153 mRNA表达均明显高于对照组,5、10 μmol/L氯化镉处理组gadd45β mRNA表达明显高于对照组,差异有统计学意义(P<0.05).结论 氯化镉可诱导HepG2细胞DNA损伤,较低剂量氯化镉即使未引起明显的DNA损伤,亦可促进HepG2细胞gadd153和gadd45β启动子和mRNA的表达.

Abstract：

Objective To investigate the effects of the cadmium chloride on the DNA damage and the expression of the gadd153 and gadd45β promoter and mRNA in HepG2 cells.Methods DNA damage induced by cadmium chloride was detected by comet assay.The plasmids (pGADD153-Luc and pG45-Luc ) containing DNA damage and repair inducible gene 153 and 45 (gadd153 and gadd45β) promoter and luciferase and gadd45β reporter gene were constructed.The activity of gadd 153 and gadd45β promoter were represented by the luciferase activity,the inducible luciferase activities was detected by bioluminescence.The expression of gaddl53 and gadd45β mRNA was detected by RT-PCR.Results The results of comet assay indicated that Olive Tail Moment induced by the cadmium chloride increased significantly at the dose of 100,300 μmol/L,compared with the control (P<0.05).The luciferase activity analysis showed that the expression levels of gaddl53 promoter increased significantly in 1,5,10 μmol/L treatment group,compared with the control (P<0.05).The expression levels of gadd45β promoter in 5,10μmol/L treatment group were significantly higher than that in control group (P<0.05).The expression levels of gaddl53 mRNA induced by cadmium chloride at the doses of 1,5,10 μ-mol/L and the expression levels of gadd45β mRNA induced at the doses of 5,10μmol/L were significantly higher than thoae in control group (P<0.05).Conclusion The cadmium chloride can induce the DNA damage and increase the expression levels of the gaddl53 and gadd45β promoters in HepG2 cells.     

Comparison of Selenium bioaccumulation in the clams Corbicula fluminea and Potamocorbula amurensis: a bioenergetic modeling approach

Selenium uptake from food (assimilation efficiency) and dissolved phase (influx rate) as well as loss kinetics (efflux rate) were compared between two bivalves, Corbicula fluminea and Potamocorbula amurensis. The effects of salinity and temperature on these kinetic parameters for both clam species also were evaluated. The Asiatic clam, C. fluminea, more efficiently assimilated Se associated with algae (66-87%) than Se associated with oxic sediments (20-37%). However, no consistent difference was found between Se assimilation efficiencies from both food types (19-60%) for P. amurensis. The temperature and salinity had a minor influence on the Se assimilation from ingested food. However, the effects of temperature and salinity were more evident in the uptake from dissolved sources. The influx rate of Se(IV) increased by threefold with the increase of temperature from 5 to 21 degrees C for C. fluminea. The increase of salinity from 4 to 20 psu decreased the uptake rate constant (ku) of Se in P. amurensis from 0.011 to 0.005 L/g/h, whereas salinity change (0-8 psu) had a negligible effect on the Se influx rate of C. fluminea. The Se influx rate of P. amurensis decreased by half with the 3.5-fold increase in tissue dry weight. The rate constant of loss was greater for P. amurensis (0.029/d at 8 psu) than for C. fluminea (0.014/d at 0 psu and 0.01/d at 8 psu). A bioenergetic model suggests that dietary uptake is the dominant pathway for Se bioaccumulation in the two clams in San Francisco Bay and that interspecies differences in Se bioaccumulation can be explained by differences in food ingestion rates.     

汾河流域水重金属含量与因肿瘤死亡构成比关系

目的探讨汾河流域水重金属含量与因肿瘤死亡构成比关系。方法通过疾病控制中心收集2009年和2010年汾河流域死因监测数据,按死因分为两组：因肿瘤死亡和非肿瘤死亡。测定2008—2010年汾河流域重金属镉、铅、铜、锌含量（mg／L）。采用SPSS13．0建数据库并进行统计描述及检验。结果因肿瘤死亡人数由2009年的第三位上升到2010年的第二位;2010年因肿瘤死亡构成比（22．26％）显著高于2009年（17．65％）。2009年镉含量（0．00775mg／L）高于2008年（0．00100mg／L）和2010年（0．00394mg／L）;2010年铅含量（0．06630mg／L）高于2008年（0．01000mg／L）和2009年（0．01000mg／L）。因肿瘤死亡构成比与铅含量呈显著性正相关（r=0．846）。结论水环境铅暴露可能是引发肿瘤的危险因素之一。建议在铅污染高危地区将血铅检测作为常规指标,定期检测,同时增加锌摄人量,以降低机体中铅含量,减少肿瘤疾病发生的危险性。     

Acute Toxicity of Aqueous Copper,Cadmium, and Zinc to the Mayfly <Emphasis Type="Italic">Rhithrogena hageni</Emphasis>

Heptageniid mayfly nymphs have been suggested as sensitive indicators of metal contamination in streams based on biomonitoring studies, experimentation in situ, and experimentation in microcosm. Laboratory tests were conducted to evaluate the sensitivity of Rhithrogena hageni, a heptageniid mayfly, to waterborne copper, cadmium, and zinc. Tests were conducted with soft water (hardness = 40–50 mg/L) at about 12°C. Toxicity endpoints were survival and moulting (%/day). Median 96 hr lethal concentrations were 0.137, 10.5, and 50.5 mg/L for copper, cadmium and zinc, respectively. The average daily moulting rate of survivors significantly decreased after exposure to these metals in solution.     

Estimation of potential and limits of bivalve closure response to detect contaminants: application to cadmium

Bivalve closure responses to detect contaminants have often been studied in ecotoxicology as an aquatic pollution biosensor. We present a new laboratory procedure to estimate its potential and limits for various contaminants and animal susceptible to stress. The study was performed in the Asiatic clam Corbicula fluminea and applied to cadmium. To take into account the rate of spontaneous closures, we integrated stress problems associated with fixation by a valve in common apparatus and the spontaneous rhythm associated with circadian activity to focus on conditions with the lowest probability of spontaneous closing. Moreover, we developed an original system by impedance valvometry, using light-weight impedance electrodes, to study free-ranging animals in low-stress conditions and a new analytical approach to describe valve closure behavior as a function of response time and concentration of contaminant. In C. fluminea, we show that cadmium concentrations above 50 microg/L can be detected within less than 1 h, concentrations down to 16 microg/L require 5 h of integration time, and values lower than 16 microg/L cannot be distinguished from background noise. Our procedure improved by a factor of six the cadmium sensitivity threshold reported in the literature. Problems of field applications are discussed.     

二(噁)英对成骨肉瘤细胞的凋亡及胰岛素样生长因子结合蛋白6表达的影响

目的 探讨二(噁)英(TCDD)对调控成骨肉瘤细胞(SaOS-2)凋亡和胰岛素样生长因子结合蛋白6(insulin-like growth factor binding protein 6,IGFBP-6)基因表达的影响.方法 应用1×10-9、1×10-8、1×10-7 mol/L浓度的TCDD作用于SaOS-2细胞株,采用四甲基偶氮噻唑蓝(MTT)法检测TCDD对SaOS-2细胞增殖能力的影响,流式细胞仪检测SaOS-2细胞株细胞凋亡率,采用对硝基酚磷酸盐法测定SaOS-2细胞内碱性磷酸酶(ALP)的活力,采用反转录-聚合酶链反应(RT-PCR)半定量分析SaOS-2中IGFBP-6 mRNA的表达,采用Western印迹杂交鉴定SaOS-2中IGFBP-6蛋白的表达.结果 在1×10-9、1×10-8、1×10-7 mol/L TCDD浓度下SaOS-2的增殖指数分别为18.4±4.5、22.5±3.6、29.4±4.2,SaOS-2 ALP的活力分别为1.12±0.28、1.58±0.14、1.96±0.17 U/mg Pro,均高于对照组;且1×10-7、1×10-8 mol/L组与对照组比较,差异有统计学意义(P＜0.05);1×10-7 mol/LTCDD浓度组的细胞凋亡率明显低于对照组,差异有统计学意义(P＜0.05).3个不同浓度组的mRNA表达和1×10-7 mol/L TCDD组蛋白的表达均明显低于对照组,差异有统计学意义(P＜0.05).结论 低浓度的TCDD对SaOS-2的凋亡代谢具有拮抗作用.TCDD对SaOS-2内IGFBP-6基因表达的抑制效应,可能是TCDD参与骨肿瘤发生及生长的作用机制之一.