Expression changes of cell cycle related molecules in palatal tissue of fetal mice with cleft palate induced by TCDD / 中华整形外科杂志

Objective@#The purpose of this study is to investigate the expression change of cell cycle-related molecules in platal tissue of fetal mice with cleft palate, induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD), and to explore the mechanism of cell cycle-related molecules in cleft palate.@*Methods@#In vivo, 48 pregnant mice were randomly divided into TCDD treatment group and control group with Random number table, 24 mice in each group. On the embryonic day 10.5 (E10.5), pregnant mice were orally administrated with TCDD 28 μg/kg (containing 5 μg/ml TCDD of corn oil) in TCDD treatment group. The same volume of corn oil was given to the mice in control group. The pregnant mice in each group were sacrificed on E13.5, E14.5 and E15.5, to collect the fetal palates for analysis. Fetal palates were used to extract total RNA and total protein, so as to detect the expression levels of cell cycle-related molecules, using RT-PCR and western blotting respectively. In vitro, human kidney embryo 293t (HEK293t) cells were treated with different concentrations of TCDD (0.01, 0.1, 0.5 and 1 nmol/L), and cells proliferation activity was detected using MTT assay. Statistical analysis was performed with IBM SPSS 24.0. Kolmogorov-Smimov test was used for normal distribution check, and the distribution was normal. Independent t-test was carried out among two groups. P<0.05 was considered statistically significant.@*Results@#At E13.5, E14.5 and E15.5, the expression level of interferon regulatory factor 6 (Irf6) protein were higher in the control group (1.26 ± 0.13, 1.67 ± 0.14 and 1.42 ± 0.15, respectively) compared to that in the TCDD group (0.81 ± 0.08, 1.04± 0.02 and 0.86 ± 0.12, respectively), on each time point (t value were 2.836, 3.662 and 2.867, respectively; P values were 0.0471, 0.0146 and 0.0241, respectively). The expression level of cyclin-dependent kinase inhibitor 1A (P21) protein on E13.5 and E14.5 of the control group (2.26 ± 0.21, 1.99 ± 0.21)were higher than that in the TCDD group on each time point(1.43 ± 0.12、0.93 ± 0.22), (t value were 3.398 and 3.378; P value were 0.8726 and 0.0273). The expression level of cyclin D1 in the control group (1.00±0.02, 0.94±0.03 and 1.11±0.09, respectively)were higher than that of the TCDD group (0.28±0.01, 0.33±0.06 and 0.88±0.01, respectively) on each time point (t value are were 22.53, 22.35 and 14.27, respectively, P value <0.001, <0.001 and<0.001, respectively). The expression of cyclin E1, cyclin A2, cyclin B1, CDK6, CDK2 and CDK1 in TCDD groups were higher than that of the controls (P<0.05). However, there was no significant difference of cyclin B1 on E13.5 and Cdk2 on E15.5. As treatment with TCDD (0.1 nmol/L) at 1, 2 and 3 days (0.70 ± 0.05, 1.05 ± 0.03 and 1.39 ± 0.04, respectively), the proliferation of HEK293t cells increased compared with the control group (0.49 ± 0.04, 0.98 ± 0.03 and 1.55 ± 0.02, respectively). The differences were statistically significant (t value were 2.829, 1.395 and 2.692, respectively; P value were 0.0198, 0.1320 and 0.0247, respectively).@*Conclusions@#TCDD down-regulates Irf6 and P21, and interferes with the normal expression of cell cycle-associated molecules, which in turn interferes with medial edge epithelia (MEE) cells cycle arrest and proliferation. These indicate that the disorder of spatiotemporal expression of cell cycle-related molecules during palatal development may be involved with the mechanism of TCDD-induced cleft palate..

The study of exposure levels of dioxin-like compounds in cord blood of newborns in an e-waste dismantling area in Guangdong Province / 中华预防医学杂志

Objective@#To study the pollution status of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in cord blood of newborns in an e-waste dismantling area of Guangdong Province.@*Methods@#We recruited 20 eligible mothers and newborns who could meet the inclusion criteria in local hospitals of Guiyu in 2007. The inclusion criteria included directly engaged in dismantling e-waste during pregnancy and within 1 year before pregnancy; living in the e-waste dismantling workshops or the distance between living place and the e-waste dismantling areas was ≤200 m; the father of newborn was directly engaged in electronic waste dismantling for more than 1 year; the frequency of visiting the e-waste dismantling workshop during pregnancy was ≥3 times in a week. Questionnaires and physical examinations were performed on maternal and neonatal, and cord blood was collected from newborns to detect PCDD/Fs, PCB and PBDE. The concentration level of organic pollutants was corrected by the blood lipid content, and the total toxicity equivalent was calculated. The correlation between three compounds was analyzed by Spearman correlation.@*Results@#The mothers of the 20 newborns were (23.45±3.27) years old and lived for more than 5 years. The number of one parent engaged in e-waste dismantling, the mother or father smoking, and parent engaged in e-waste dismantling work were 3, 13, 15 and 19, respectively. The weight of newborns ranged from 2.5 to 3.6 kilogram and the Apgar score was 10 points. No adverse birth outcomes such as preterm birth, malformation or stillbirth were found. The median (maximum, minimum) concentration of PCBs, PCDD/Fs and PBDEs in cord blood were 263.22 (328.29, 244.19), 38.42 (147.49, 12.68), 39.33 (265.11, 14.81) pg/g lipid, respectively. The median (maximum, minimum) of toxic equivalence concentrations of PCDD/Fs and PCB were 3.94 (9.24, 2.69) and 15.95 (26.64, 9.28) pg TEQ/g lipid. PBDE, the proportion of PBDE, PCB and PCDD/Fs in cord blood was 50.41%, 49.25% and 0.34%, respectively. PCBs and PBDEs were positively correlated (r=0.733, P=0.039).@*Conclusion@#The high concentrations of PCDD/Fs, PCB, and PBDE were detected in the e-waste dismantling area. It is recommended that the risk of such substances on the health of local people should be assessed in a timely manner.

Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan

BACKGROUND@#Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002-2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers.@*METHODS@#From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit.@*RESULTS@#The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8-9.9) pg TEQ/g lipid and 0.3 (0.2-0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011-2016 survey was found to have decreased by 41.3% compared to the 2002-2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake.@*CONCLUSIONS@#Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population.

2,3,7,8-Tetrachlorodibenzo-p-dioxin Promotes Proliferation of Astrocyte Cells via the Akt/STAT3/Cyclin D1 Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant, is harmful to the nervous system, but its effects on the brain are still unclear. This study aimed to investigate the effects of TCDD on astrocytes proliferation and underlying molecular mechanism.@*METHODS@#The cell proliferation was measured by EdU-based proliferation assay and PI staining by flow cytometry. Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of signal transducer and activator of transcription 3 (STAT3).@*RESULTS@#C6 cells treated with 10 and 50 nmol/L TCDD for 24 h showed significant promotion of the proliferation of. The exposure to TCDD resulted in the upregulation in the expression levels of phosphorylated protein kinase B (p-Akt), phosphorylated STAT3, and cyclin D1 in a dose- and time-dependent manner. The inhibition of Akt expression with LY294002 or STAT3 expression with AG490 abolished the TCDD-induced cyclin D1 upregulation and cell proliferation. Furthermore, LY294002 suppressed the activation of STAT3. Finally, TCDD promoted the translocation of STAT3 from the cytoplasm to the nucleus, and LY294002 treatment blocked this effect.@*CONCLUSION@#TCDD exposure promotes the proliferation of astrocyte cells via the Akt/STAT3/cyclin D1 pathway, leading to astrogliosis.

Down-regulation of miR-381-3p inhibits osteogenic differentiation of mouse embryonic palatal mesenchymal cells in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced cleft palate of fetal mice / 中国修复重建外科杂志

Objective: To investigate the correlation between down-regulation of miR-381-3p and inhibition of osteogenic differentiation of mouse embryonic palatal mesenchymal (MEPM) cells in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate of fetal mice. Methods: Thirty-two pregnant mice were randomly divided into TCDD group and control group, 16 in each group. On embryonic day 10.5 (E10.5), the pregnant mice in TCDD group were orally administrated with TCDD at dosage of 28 μg/kg, while the pregnant mice in control group received equivalent corn oil. The pregnant mice in each group were sacrificed on E13.5 and E14.5, fetal palates were collected for analysis. The expression of miR-381-3p was detected by real-time fluorescent quantitative PCR and the protein expressions of runt- related transcription factor 2 (RUNX2) and osteopontin (OPN) were detected by Western blot. MEPM cells were extracted from fetal palates on E14.5 in control group and passaged. The 3rd passage cells were cultured with TCDD at dosage of 10 nmol/L for 0, 0.5, 1, 2, and 3 days. The expression of miR-381-3p was detected after 0, 0.5, 1, 2, and 3 days and the protein expressions of RUNX2 and OPN were detected after 0, 1, 2, and 3 days. Then, the 3rd passage cells were divided into 4 groups. The MEPM cells were transfected with miR-381-3p inhibitor (inhibitor group), NC inhibitor (NC inhibitor group) and miR-381-3p mimics (mimics group), NC mimics (NC mimics group) for 48 hours, respectively. And the expressions of miR-381-3p and the protein expressions of RUNX2 and OPN were detected. Results: On E13.5 and E14.5, 96 fetal mice in control group and 92 in TCDD group were obtained. The bilateral palates contacted in control group on E14.5, and a gap between the bilateral palates existed in TCDD group. On E13.5 and E14.5, the relative expressions of miR-381-3p and RUNX2 and OPN proteins were significant lower in TCDD group than in control group ( P0.05). The relative expressions of RUNX2 and OPN proteins at 1, 2, and 3 days were significantly lower than that at 0 day ( P<0.05). The relative expressions of miR-381-3p and RUNX2 and OPN proteins significantly lower in inhibitor group than in NC inhibitor group ( P<0.05) and higher in mimics group than in NC mimics group ( P<0.05). Conclusion: Down-regulation of miR-381-3p expression may be associated with inhibition of osteogenic differentiation of MEPM cells in TCDD-induced cleft palate of fetal mice.

Beta-glucan prevents toxic effects of 2, 3, 7, 8-TCDD in terms of oxidative and histopathological damage in heart tissue of rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant which causes severe toxic effects. Despite there is some suggestion concerning with TCDD induced cardiotoxicity such as formation of free radicals, the main mechanism has not been entirely explained. Beta-glucan is known as strong antioxidant matter and can scavenge free radicals. Therefore this study aimed to investigate the protective effects of beta-glucan against TCDD induced cardiotoxicity in rats. In this study, 2-3 months of age and 190-250 g in weight 32 rats were randomly divided into four equal groups (n=8 for each group). Group 1 was control; Group 2 was TCDD group (2 µg/kg/week); group 3 was the beta-glucan group(50 mg/kg/day), and group 4 was TCDD and beta-glucan treatment group. The heart samples were taken from rats after 21 days treatment. The results were shown that Despite TCDD exposure visibly caused to increase (p ≤ 0.001) in TBARS levels, It caused a visible decline in the levels of GSH, CAT, GSH-Px, and SOD. However Beta glucan significantly increased GSH, CAT, GSH-Px, SOD levels and decreased generation of TBARS. Additionally, our histopathological observations were in agreement with the biochemical results. In conclusion, Beta-glucan treatment exhibited protective activity on TCDD induced cardiotoxicity

The expression change of histone H4 acetylation in TCDD-induced cleft palates formation in fetal mice / 中华整形外科杂志

Objective@#To evaluate the expression of histone H4 acetylation(Ac-H4) during the cleft palates formation induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) in C57BL/6J mice.@*Methods@#Forty-eight pregnant C57BL/6J mice were completely randomly divided into two groups: ① TCDD group, mice were treated with 20ug/kg of TCDD on gestation day (GD) 10.5 by gastric perfusion; ② control group, mice were treated with an equivalent of corn oil. The head samples were collected and sliced in coronal plane on GD13.5, GD14.5 and GD15.5 respectively. Histone H4 acetylation in the palates were evaluated by immunohistochemical staining and Western Blot in the two groups.@*Results@#Histone H4 acetylation was mainly expressed in the palatal epithelial cells and slightly expressed in mesenchymal cells. The expression level of histone H4 acetylation was 0.6002±0.2530, 0.9180±0.0941 and 0.8966±0.0908 respectively in control group on GD13.5, GD14.5 and GD15.5; while 1.0229±0.2779, 1.6095±0.2651 and 1.2758±0.1251 in TCDD group. There were statistically significant differences between the control group and TCDD group (P<0.05).@*Conclusions@#The histone H4 acetylation was involved in the cleft palate formation induced by TCDD in C57BL/6J mice.

Analysis of medication compliance of nursing intervention combined with digoxin in elderly patients with heart failure / 中国生化药物杂志

Objective To analyze nursing intervention and digoxin treatment of elderly heart failure patients taking digoxin drug compliance reasons. Methods Select Red Cross Hospital of Hangzhou on March 21, 2015 to March 21, 2016, 110 cases of senile heart failure patients as the research object, take the envelope random grouping scheme, divided into normal group and experimental group two groups, each group are occupying 55 cases. Among them to digoxin therapy on conventional therapy alone, in the experimental group were markedly drug treatment and corresponding nursing intervention, compared two groups of patients' medication compliance and quality of life score. Results the patients in the experimental group were 98.18% and 81.82% respectively, and the comparison groups were significantly different(P<0.05). The experimental group after treatment the patient's quality of life score of each dimension (physical function, psychological state, the doctor-patient relationship, independence, social relations, the personal faith and the general quality of life) were significantly better than the conventional group(P<0.05). Conclusion For elderly patients with heart failure to take scientific and reasonable method for nursing to improve the adherence of digoxin drugs, improve the quality of life, is worth popularizing practice.

Identification of differentially expressed proteins of palate tissues by iTRAQ in fetal mice induced by TCDD or retinoic acid / 中华整形外科杂志

Objective@#To explore the common differentially expressed proteins in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) and retinoic acid-induced cleft palate of fetal mice by isobaric tags for relative and absolute quantitation(iTRAQ) combined with mass spectrometry.@*Methods@#Thirty-six pregnant C57BL/6J mice were randomly divided into 3 groups, 12 cases in each group. C57BL/6J pregnant mice were given a gavage of TCDD 28 μg/kg or retinoic acid 80 mg/kg on gestational day 10.5(GD10.5) as experimental groups, while the control group received equivalent corn oil. Anatomical and histological changes of palates in fetal mice were observed on GD17.5. Total proteins were extracted from palates of fetal mice in each group on GD17.5. Differentially expressed proteins were identified in experimental groups as well as in control group by iTRAQ combined with two-dimensional liquid chromatography/tandem mass spectrometry. Western Blot was used for validation of the differentially expressed proteins of Annexin A1 and 14-3-3 sigma. All statistical analyses were measured with SPSS software(version 17.0). Chi-square test was used to compare the incidence of cleft palate. One-way ANOVA was carried out for comparison of the relative expression levels of three groups, homogeneity of variance was analyzed by Levene test, and Turkey HSD test was used for comparison between two groups. P values were judged as significant difference if they were less than 0.05.@*Results@#①Model of cleft palate in fetal mice were successfully established with incidence of cleft palate of 97.1%(68/70)in TCDD group and 98.6%(70/71) in retinoic acid group, respectively(χ2=0.00, P>0.05), without significant difference between two groups. However, they were similar on the phenotype. ② A total of 2 996 proteins were identified. Compared with control group, 75 and 90 differentially expressed proteins were screened out from TCDD group and retinoic acid group respectively. There were 18 differentially expressed proteins in common both in two experimental groups. ③Western Blot assay indicated that the expression of Annexin A1 protein was 0.52±0.11 in control group, while in TCDD group was 0.99±0.34 and in retinoic acid group was 0.98±0.31, with significant difference between any of two experimental groups and control group(P<0.05). The expression of 14-3-3 sigma protein in control group was 0.55±0.15, while in TCDD group was 0.86±0.17 and in retinoic acid group was 0.93±0.13, with significant difference between any of two experimental groups and control group(P<0.05). These results were consistent with the results of iTRAQ experiment.@*Conclusions@#Using iTRAQ technology can quickly and effectively filtrate the common differentially expressed proteins in fetal mice with cleft palate induced by TCDD and retinoic acid. These proteins may have closely related relationship with the occurrence of cleft palate induced by TCDD or retinoic acid.

3-D reconstruction of tetrachlorodibenzo-p-dioxin effected palatal organ development model of fetal mouse / 实用口腔医学杂志

Objective:To study the feasibility of 3-D reconstruction model in the observation of tetrachlorodibenzo-p-dioxin(TCDD) effected palatal organ development of fetal mouse.Methods:Kunming mice treated 40 ug/kg TCDD by lavage on day 12.5 of pregnancy were used as in the experimental group,isodose corn oil treated in the control group.On day 13.5,14.5 and 15.5 of pregnancy heads of the fetal mice were taken out and fixed.Conventional paraffin serial sections of palatal organ were preparated and dyed by hematoxylin-eosin,images of the palatal organs were collected and photoshop treated,3-D reconstruction of the palatal organ was performed by 3D-DOCTOR software.Results:3-D reconstruction images showed that palatal organs moved from on both sides above the tongue and gradually closed and merged in the control group.In the experimental group,the palatal organs moved from on both sides above the tongue was later than control group,gradually closed,but not merged,formed cleft palate.Conclusion:3D-DOCTOR software reconstruction can be used for the study of the development process effected by TCDD in the pregnant mouse.

Design of on-board medical waste pyrolysis furnace / 医疗卫生装备

Objective To design an on-vehicle medical waste pyrolysis furnace for the safe disposal of medical wastes, which could disposal 1t wastes each day. Methods A furnace was designed by in-depth research of pyrolysis, calculation analysis in detail, and taking the experimental results and other factors in. The flue gas treatment system of this medical waste pyrolysis furnace was designed through 3T principle.Results This furnace behaved well in configuration, reliability and self support, whose dioxin emission was limited as 0.213 ng/m3.Conclusion The on-vehicle medical waste pyrolysis furnace gains advantages in safety and environment protection, and has a brilliant future in practice.

Determination of Polychlorinated Dibenzo-p-dioxins/Dibenzofurans, Dioxin Like Polychlorinated Biphenyls, Brominated Flame Retardants and Polybrominated Dibenzo-p-dioxins/Dibenzofurans in Flue Gas from Stationary Source / 分析化学

A method for simultaneous determination of PCDDs, dl-PCBs, BFRs and PBDD/Fs in flue gas from stationary source was developed. The sample was extracted by Soxhlet apparatus with toluene, and followed by purification through sulfuric acid partition and multi-layer silica gel column separation. The target compounds were then all separated by passing through the active carbon-dispersed silica gel column and reversal eluting. Gas chromatography coupled with a thermostable capillary column ( short length, thin stationary phase film) was operated at pulse injection mode. High resolution mass spectrometry set at low-electron-energy ionization was used for quantification. The high- and low-brominated compounds were determined simultaneously. The detection limits of this method were 0. 081-1. 2 pg for PCDD/Fs, 0. 10-0. 32 pg for dl-PCBs, 0. 14-12 pg for PBDEs, 0. 26-16 pg for new BFRs, 0. 44-3. 6 pg for tetra- to hepta-BDD/Fs and 8. 2-12 pg for OBDD/F. Recoveries ( RSDs) in spiked flue gas samples were 88%-115%(2. 9%-6. 1%) for PCDD/Fs, 84%-118% (3. 2%-10%) for dl-PCBs, 71%-135% (2. 1%-18%) for PBDEs, 71%-114% (2. 9%-7. 4%) for new BFRs, 83%-127% (5. 2%-10%) for tetra-to hepta-BDD/Fs and 52%-149% ( 23%-24%) for OBDD/F. All quality control data fell within the acceptable range specified in analysis standards for flue gas.

Application research on new technology for on-board medical waste pyrolysis / 医疗卫生装备

Objective To explore the theories of medical waste pyrolysis system composition, waste pyrolysis process, flue gas treatment process and etc.Methods The composition and process of pyrolysis treatment system and flue gas cleaning system were studied with the theories of configuration design, physico-chemical analysis, thermodynamics, fluid mechanics and etc.Results The schemes were put forward for on-board pyrolysis furnace and flue gas cleaning system.Conclusion On-board medical waste pyrolysis system can be used to treat the infectious waste in public medical emergencies, and thus is worth popularizing practically.

The Benefit Risk Assessment of Consumption of Marine Species Based on Benefit-Risk Analysis for Foods (BRAFO)-tiered Approach / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the net health effect caused by the consumption of specific marine species based on Benefit-Risk Analysis for Foods (BRAFO)-tiered approach.</p><p><b>METHODS</b>Twenty species were collected from the Zhoushan Archipelago, China. Concentrations of n-3 long-chain polyunsaturated fatty acids, methyl mercury (MeHg), and dioxin-like compounds (DLCs) in the samples were analyzed for benefit risk assessment based on BRAFO-tiered approach.</p><p><b>RESULTS</b>Based on the BRAFO-tiered approach, reference scenario (no intake) and alternative scenario (intake of specific species of 200 g/week) were determined. The exposure to MeHg/DLCs via alternative scenario of all studied species did not exceed provisional tolerable weekly/monthly intake. However, the adult population with high DLCs exposure in China would significantly exceed the upper limit of DLCs via an additional alternative scenario of some species such as Auxis thazard. The results of deterministic computation showed that alternative scenario of all studied species generated clear net beneficial effects on death prevention and child IQ gain.</p><p><b>CONCLUSION</b>The alternative scenario of all studied species could be recommended to population with average DLCs exposure, and the reference scenario of species with relatively high DLCs concentration could be recommended to population exposed to high DLCs.</p>

Risk and culture: variations in dioxin risk perceptions, behavioral preferences among social groups in South Korea

OBJECTIVES: This study examined variations in the perceptions of dioxin risk among social groups defined by geographical living location, environmental education, and occupation. Dioxin risk perceptions were analyzed according to values, risk awareness, knowledge, and behavioral preferences. METHODS: A quasi-experimental survey was designed and conducted on individuals from seven experimental groups in Jeonju city, South Korea, including: people living near incineration facilities; people living far from incineration facilities; governmental experts; nongovernmental organization members; office workers in developmental institutes or banks; students who were enrolled in environmental-related classes; and students who were enrolled in business-related classes. RESULTS: The results show variations among groups in values, awareness and behavioral preferences. Particular attention should be given to the result that groups with higher connectedness- to-nature values show higher willingness-to-act (WTA) for risk reduction. Result s can be summarized as follows. First, awareness is associated with one's geographical setting. Second, values and WTA behaviors are related to one's environmental-related education and occupation. Third, values are significantly related to WTA behaviors. CONCLUSIONS: Different cultures, in terms of values or worldview, among groups influence their perceptions of dioxin risk and choices of risk reduction behaviors. It is important to consider values in communicating complicated long-term risk management involving public participation. Further research should be continuously conducted on the effects of multiple dimensions of values on one's WTA for risk reduction behaviors.

Synergistic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and N-nitrosodiethylamine on cell malignant transformation / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N-nitrosodiethylamine (DEN) on tumorigenesis and its potential mechanism.</p><p><b>METHODS</b>The potentials of TCDD and DEN in separation or in combination to induce malignant transformation were tested in Balb/c 3T3 cells by using a cell transformation assay method. The possible mechanism of observed effects was studied further by adding α-naphthoflavone (α-NF), a competitive binding agent of TCDD, to the Aryl hydrocarbon receptor (AhR) pathway. The mRNA expressions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separation or in combination with or without presence of α-NF were measured with fluorescence quantification RT-PCR technique.</p><p><b>RESULTS</b>The cell transformation frequency (TF) was significantly higher in case of induction with TCDD in combination with DEN, as compared to that with either TCDD or DEN alone. These effects were not inhibited via α-NF. The mRNA expression levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment alone, but this inducible effect was blocked in cells treated by TCDD and DEN in combination.</p><p><b>CONCLUSION</b>TCDD and DEN had a significant synergistic effect on tumorigenesis when they were used in combination. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.</p>

Effect of tetrachlorodibenzo-p-dioxin on the expression of cytochrome P4501A1 in human SZ95 sebocytes and its significance / 中华皮肤科杂志

Objective To estimate the effect of the enviromental pollutant 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD),a representative of the dioxin family,on the expression of cytochrome P4501A1 (CYP1A1) in cultured human immortalized SZ95 sebocytes in vitro,so as to improve understanding of the pathogenesis of chloracne.Methods SZ95 sebocytes were cultured with or without the presence of 10 nmol/L TCDD for two hours or three days.Real time fluorescence-based PCR was performed to quantify the mRNA expression of CYP1A1,immunohistochemistry and Western blot to determine the expression level of CYP1A1 protein,in the SZ95 cells.Chi-square test was done to compare the protein and mRNA expressions of CYP1A1 between untreated and treated SZ95 cells.Results Real time PCR showed that the mRNA expression of CYP1A1 was low in SZ95 sebocytes,and increased by 5.622 times after 2-hour treatment with TCDD(P ＜ 0.05).Immunohistochemistry revealed a weak expression of CYP1A1 protein in the cytoplasm and nuclei of untreated SZ95 sebocytes,which was also significantly enhanced by the TCDD treatment.Western blot results showed that the relative expression level of CYP1A1 protein was 4.233 ± 0.252 in SZ95 sebocytes treated by TCDD for three days,significantly higher than that in untreated sebocytes(0.123 ± 0.208,P ＜ 0.05).Conclusions There is a low expression of CYP1A1 mRNA and protein in SZ95 sebocytes,which can be upregulated by TCDD,suggesting that the CYP1A1 gene is a downstream target of the aryl hydrocarbon receptor responsible for the abnormal differentiation of human sebocytes.

Induction of Heat Shock Proteins and Antioxidant Enzymes in 2,3,7,8-TCDD-Induced Hepatotoxicity in Rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, alpha-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (alpha-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

Dioxin-induced changes in epididymal sperm count and spermatogenesis / Mudanças induzidas por dioxina na contagem epididimal de esperma e espermatogênese

A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we postulate that epididymal function is the key target for the adverse effects of TCDD.

Uma única exposição in utero a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) no 15º dia de gestação diminuiu a contagem de esperma epididimal em ratos adultos e por isso foi utilizada para estabelecer uma dosagem diária tolerável para TCDD. No entanto, diversos laboratórios não conseguiram reproduzir esses resultados. Além disso, relatórios conflitantes dos efeitos de TCDD na produção diária de esperma sugere que espermatogênese pode não ser tão sensível aos efeitos adversos do TCDD como antes se pensava. Foi feita uma pesquisa no PubMed usando termos de pesquisa relevantes, relacionados à exposição à dioxina com efeitos adversos na reprodução e na espermatogênese. Exposição em desenvolvimento ao TCDD é consistentemente relacionada à diminuição da contagem da cauda epididimal de esperma, mas não apoia a conclusão de que a espermatogênese é afetada. Os mecanismos por trás da diminuição da contagem de esperma epididimal são desconhecidos; no entanto, contestamos que a função epididimal é a chave para efeitos adversos do TCDD.

Mitochondrial Dysfunction and Insulin Resistance: The Contribution of Dioxin-Like Substances

Persistent organic pollutants (POPs) are known to cause mitochondrial dysfunction and this in turn is linked to insulin resistance, a key biochemical abnormality underlying the metabolic syndrome. To establish the cause and effect relationship between exposure to POPs and the development of the metabolic syndrome, Koch's postulates were considered. Problems arising from this approach were discussed and possible solutions were suggested. In particular, the difficulty of establishing a cause and effect relationship due to the vagueness of the metabolic syndrome as a disease entity was discussed. Recently a bioassay, aryl-hydrocarbon receptor (AhR) trans-activation activity using a cell line expressing AhR-luciferase, showed that its activity is linearly related with the parameters of the metabolic syndrome in a population. This finding suggests the possible role of bioassays in the analysis of multiple pollutants of similar kinds in the pathogenesis of several closely related diseases, such as type 2 diabetes and the metabolic syndrome. Understanding the effects of POPs on mitochondrial function will be very useful in understanding the integration of various factors involved in this process, such as genes, fetal malnutrition and environmental toxins and their protectors, as mitochondria act as a unit according to the metabolic scaling law.