Quantitative risk assessment of occupational exposure to PCDD/Fs in the waste incineration industry / 中华劳动卫生职业病杂志

Objective: To analyze the level of PCDD/Fs exposure of occupational workers in the waste incineration industry and explore the risk of occupational exposure. Methods: In September 2021, literature on environmental PCDD/Fs exposure in waste incineration plants published from the establishment of the database to February 10, 2021 was retrieved from CNKI database. A total of 1365 literatures were retrieved, and 7 met the criteria for inclusion. The US Environmental Protection Agency (EPA) inhalation risk model was used to assess and analyze carcinogenic and non-carcinogenic risks of PCDD/Fs exposure among occupational workers in the waste incineration industry. Results: A total of 86 sampling sites were included in incineration plants in 7 regions. The study of Wuhan area showed that the concentration of working environment near the waste incinerator in the same factory was the highest, followed by the rest and office area in the factory. The concentration of PCDD/Fs in waste incinerators was the highest in Southwest China (4880.00-24880.00 pg TEQ/m(3)), and the lowest in Shenzhen (0.02-0.44 pg TEQ/m(3)). According to the cancer risk assessment, with the increase of exposure years, the risk of cancer increased. The highest risk of cancer was found in the waste incineration plants in Southwest China. When the exposure period was 1 year, the risk was moderate (22.40×10(-6)-114.20×10(-6)). When the exposure time was more than 5 years, the risk of cancer was high. In Jinan, workers working near the incinerator had a moderate risk of cancer after five years of exposure. In Zhejiang, workers were at medium risk of cancer after exposure for more than 20 years. Workers in Wuhan, Shanghai, Zhejiang Province, Shenzhen and the Pearl River Delta were still at low risk of cancer after 40 years of occupational exposure. HQ>1 of workers working near the waste incinerators in Jinan, Zhejiang Province and Southwest China, and the qualitative evaluation results showed that the non-carcinogenic risk was unacceptable. Conclusion: There are great differences in PCDD/Fs of occupational exposure in waste incineration industry, and the occupational exposure exceeding the occupational exposure limit has higher carcinogenic and non carcinogenic risks.

Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin / 中华口腔医学杂志

Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 μg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-β receptor Ⅰ (TGF-βRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-βRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-βRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.

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.

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

LncRNA H19 and Target Gene-mediated Cleft Palate Induced by TCDD / 生物医学与环境科学（英文）

This study investigated the role of long non-coding RNAs (lncRNAs) in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression levels of long non-coding RNA H19 (lncRNA H19) and insulin-like growth factor 2 (IGF2) gene were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The rate of occurrence of cleft palate was found to be 100% by TCDD exposure, and TCDD could cause short upper limb, cerebral fissure, webbed neck, and short neck. The expression levels of lncRNA H19 and IGF2 gene specifically showed embryo age-related differences on E13, E14, and E15 in the palatal tissues. The expression levels of lncRNA H19 and IGF2 gene showed an inverse relationship on E13, E14, and E15. These findings demonstrated that lncRNA H19 and IGF2 can mediate the development of mouse cleft palate.

The beneficial effects of Montelukast against 2 3 7 8 tetrachlorodibenzo dioxin toxicity in female reproductive system in rats

ABSTRACT PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

Effect of 1, 2, 3, 4, 6, 7, 8, 9-octachlorodibenzo-p-dioxin on testicular gene expression profiles in male mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD) on the testicular gene expression profile in the testis of mice.</p><p><b>METHODS</b>Twenty male C57BL/6j mice were randomly divided into normal control group (fed with maize oil) and 3 OCDD groups treated with OCDD by gavage for 30 days at low-, moderate-, and high doses of 1.25×10(-6), 1.25 ×10(-5), and 1.25×10(-4) g/mL, respectively (8 mL/kg daily). The testicular gene expression profiles of the mice were investigated using gene chip technique and compared between OCDD-exposed groups and the control group.</p><p><b>RESULTS</b>Compared with the control group, the mice in low-dose OCDD group showed 1133 differentially expressed genes, including 659 up-regulated and 474 down-regulated ones; in the moderate-dose OCDD group, 978 genes were differentially expressed, including 487 up-regulated and 491 down-regulated ones; in the high-dose group, 895 genes were differentially expressed, including 424 up-regulated and 471 down-regulated ones.</p><p><b>CONCLUSION</b>The effect of sub-chronic exposure to OCDD on testicular gene expression profiles in male C57BL/6j mice indicates that the testis is probably the target organ of OCDD.</p>

Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation / 결핵및호흡기질환

BACKGROUND: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. METHODS: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. RESULTS: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. CONCLUSION: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

Tetrachlorodibenzo-p-dioxin-induced cleft palate because of partial loss of cell polarity to interfere with apoptosis during early developmental stage / 中华口腔医学杂志

<p><b>OBJECTIVE</b>In this study, folic acid (FA) was tested for antiteratogenic effects on Tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice.</p><p><b>METHODS</b>In the present study, pregnant mice were dosed with TCDD 24 µg/kg and with or without FA 5 mg/kg body weight on gestation day 10. Control group mice received sesame oil 50 ml/kg body weight on gestation day(GD)10. The mice were sacrificed on GD12.5, GD13.5, GD14.5, GD15.5 and GD16.5. From each pregnant mouse on GD16.5, embryos were obtained to examine under a dissecting microscope, and routine histology was performed for detection and classification of palatal clefts. The fetuses were prepared for histologic examination, scanning electron microscope and TdT-mediated X-dUTP nick and labeling (TUNEL). On GD12.5, GD13.5, GD14.5 and GD15.5. Meanwhile, real-time (RT)-PCR was employed to detect the mRNA expression levels about arylhydrocarbon receptor (AHR) and transforming growth factor (TGF)β3 in this animal model.</p><p><b>RESULTS</b>Total frequencies of clefts were 70.2% in TCDD group(group B) and 66.3% in TCDD+FA group(group C) in relation to control fetuses(group A). Filopodia disappeared completely at the medial edge epithelia surface on GD15.5 (group A), GD12.5 (group B) and GD14.5 (group C). the RT-PCR results showed that TGF -β3 expression was down-regulated on GD13.5 and GD14.5 compared to the control.</p><p><b>CONCLUSIONS</b>It is found that folic acid has no protects agaist 2.3.7.8-TCDD-indued cleft palate in the experiment. Meanwhile, TCDD repressed the TGF-β3 expression during the palatal development. Anormal apoptosis was induced by 2, 3, 7, 8-TCDD at the medial edge epithelia (MEE) during the early development stage.</p>

The role of histone H3 acetylation on cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzopdioxin / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the role of histone H3 acetylation in cleft palate induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice, and its mechanism.</p><p><b>METHODS</b>On gestation day 10 (GD10), 36 pregnant mice were randomly divided into two groups as the treated group(n = 18) and the control group( n = 18). The mice in the treated group received intragastric administration with TCDD 28 μg/kg, while the mice in the control group received equivalent corn oil. The pregnant mice were sacrificed on GD13. 5, GD14. 5 and GD15. 5, collecting fetal palates to determine the activities of histone acetyltransferases (HATs) by Colorimetric and the expression level of acetylated histone H3 (Acetylated histone H3, Ac-H3) by Western-blot.</p><p><b>RESULTS</b>The activity of HATs was 0.409 7 ± 0.0147, 0.522 3 ± 0.017 1 and 0.643 5 ± 0.013 9 in control group on GD13.5, GD14.5 and GD15.5; 0.865 0 ± 0.0129, 0.719 1 ± 0.017 8 and 0.551 2 ± 0.016 8 in TCDD group. The activity of HATs in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference between the two groups (t = - 56. 932, t = - 19. 516, P < 0.01); however, the activity of HATs in TCDD group was significantly lower than that in control group on GD15. 5 (t = 10. 382, P < 0.01). The expression level of Ac-H3 was 0.745 0 ± 0.113 5, 1.055 9 ± 0.249 4 and 1.795 5 ± 0.081 9 in control group on GD13. 5, GD14. 5 and GD15. 5; while 1.4490 ± 0. 1460, 1. 641 8 ± 0.099 7 and 1. 512 1 ± 0. 150 2 in TCDD group. The expression of Ac-H3 in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference( t = -6. 593, -3. 779, P <0. 01, P <0.05) ; However, the expression of Ac-H3 in TCDD group was statistically lower than that in control group (t = 2. 870, P <0. 05).</p><p><b>CONCLUSION</b>The acetylation of histone H3 was involved in the cleft palate of C57BL/6J mice induced by TCDD, which may be one of the mechanisms in TCDD-induced cleft palate.</p>

2,3,7,8-Tetrachlorodibenzo-P-Dioxin Induced Cell-Specific Drug Transporters With Acquired Cisplatin Resistance in Cisplatin Sensitive Cancer Cells

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce drug transporter genes such as the ATP-binding cassette G member 2 (ABCG2), which contributes to multidrug resistance. We investigated the effect of TCDD pretreatment on drug transporters induction from cancer cells of various origins. Cell viabilities after treatment of cisplatin were measured to evaluate acquiring cisplatin resistance by TCDD. Acquring cisplatin resistance was found only in cisplatin senstivie cancer cells including gastric SNU601, colon LS180, brain CRT-MG and lymphoma Jurkat cells which showed a significant increase in cell viability after combined treatment with TCDD and cisplatin. High increase of ABCG2 gene expression was found in SNU601 and LS180 cells with a mild increase in the expression of the ABCC3, ABCC5,and SLC29A2 genes in SNU601 cells, and of major vault protein (MVP) in LS180 cells. The AhR inhibitor kaempferol suppressed the upregulation of ABCG2 expression and reversed the TCDD-induced increase in cell viability in LS180 cells. However, in CRT-MG cells, other transporter genes including ABCC1, ABCC5, ABCA3, ABCA2, ABCB4, ABCG1, and SLC29A1 were up-regulated. These findings suggested the acquiring cisplatin resistance by TCDD associated with cancer cell-type-specific induction of drug transporters.

2,3,7,8-Tetrachlorodibenzo-P-Dioxin Induced Cell-Specific Drug Transporters With Acquired Cisplatin Resistance in Cisplatin Sensitive Cancer Cells

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce drug transporter genes such as the ATP-binding cassette G member 2 (ABCG2), which contributes to multidrug resistance. We investigated the effect of TCDD pretreatment on drug transporters induction from cancer cells of various origins. Cell viabilities after treatment of cisplatin were measured to evaluate acquiring cisplatin resistance by TCDD. Acquring cisplatin resistance was found only in cisplatin senstivie cancer cells including gastric SNU601, colon LS180, brain CRT-MG and lymphoma Jurkat cells which showed a significant increase in cell viability after combined treatment with TCDD and cisplatin. High increase of ABCG2 gene expression was found in SNU601 and LS180 cells with a mild increase in the expression of the ABCC3, ABCC5,and SLC29A2 genes in SNU601 cells, and of major vault protein (MVP) in LS180 cells. The AhR inhibitor kaempferol suppressed the upregulation of ABCG2 expression and reversed the TCDD-induced increase in cell viability in LS180 cells. However, in CRT-MG cells, other transporter genes including ABCC1, ABCC5, ABCA3, ABCA2, ABCB4, ABCG1, and SLC29A1 were up-regulated. These findings suggested the acquiring cisplatin resistance by TCDD associated with cancer cell-type-specific induction of drug transporters.

Protective role of curcumin against 2,3,7,8-tetrachlorodibenzo-dioxin-induced histological and biochemical changes in fundic mucosa of the adult rat stomach

2,3,7,8-Tetrachlorodibenzo-dioxin [TCDD] is released into the environment from different activities and industrial sources, with a higher incidence of gastric exposure. This work aimed to study the histological and biochemical changes induced by TCDD in the fundic mucosa and the possible protective role of curcumin against these changes. Thirty adult female albino rats were classified into three groups: the control group [group I]; the TCDD group [group II], in which rats received 100 microg/kg TCDD orally for 3 months; and the curcumin+TCDD group [group III], in which rats received an oral dose of 80 mg/kg curcumin in concurrence with TCDD for 3 months. The serum level of the gastrin hormone was measured. Samples from the fundus of the stomach were stained with H and E, Van Gieson, and PAS/alcian blue and for immunohistochemical detection of aryl hydrocarbon receptors [AHR] and chromogranin A. Morphometric and electron microscopic studies were also carried out. Hyperplasia and metaplastic mucosal changes, together with enteroendocrine cell hyperplasia, were evident. Moreover, glandular degeneration, areas of atrophic gastritis, cellular apoptosis, and gastric ulcers were detected. The previous results could be explained by both TCDD-induced hypergastrinemia and increased AHR expression. In contrast, curcumin appeared to have a propitious protective effect against TCDD-induced gastric affection. Most of the TCDD-induced gastric changes were not observed in group III. It was concluded that the gastric mucosa is sensitive to the toxic effects of TCDD and curcumin can be used to avoid TCDD-induced gastric complications

Activation of aryl hydrocarbon receptor prolongs survival of fully mismatched cardiac allografts / 华中科技大学学报（医学）（英德文版）

Recent data suggest that activation of aryl hydrocarbon receptor (AhR) by its high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in expansion of regulatory T (Treg) cells and suppresses the development of autoimmune and allergic diseases in several models. Treg cells have been increasingly documented to suppress allograft rejection and even to establish stable long-term graft acceptance. However, the involvement of TCDD in the regulation of solid organ transplantation rejection is largely unknown. Here, we examined whether activation of AhR with TCDD altered cardiac allograft rejection in an allogeneic heart transplant model. Recipient C57BL/6 (H-2b) mice were administrated with a single intraperitoneal injection of TCDD, and the murine cardiac transplant models from BALB/c (H-2d) to C57BL/6 (H-2b) were built 24 h later. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of TCDD on T-cell proliferation was assessed by mixed lymphocyte reaction (MLR). Histological and immunohistochemical analyses were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Activation of AhR remarkably prolonged the survival of cardiac allografts to more than 20 days. In vitro, TCDD ugregulated the frequency of CD4+CD25+Foxp3+ Treg cells and suppressed the proliferation of T lymphocytes. In vivo, the prolonged survival time was associated with increased number of Treg cells in allografts and spleens. Furthermore, the secretion of interferon-γ (IFN-γ) and interleukin-17 (IL-17) was reduced to less than 50% of that of the PBS treatment control group by TCDD treatment, whereas IL-10 was elevated to 10-fold of that of the PBS treatment control group. Collectively, our data indicate that activation of AhR with a single dose of TCDD significantly prolonged the survival of fully allogeneic cardiac grafts, and the mechanism underlying this effect might be involved in the induction of Treg cells.

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>

The human body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls in residents' human breast milk from Beijing in 2007 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate contamination levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in human breast milk from Beijing residents, and evaluate the human body burden of PCDD/Fs and dl-PCBs of general population.</p><p><b>METHODS</b>A total of 110 human milk samples were collected from 11 regions in Beijing in 2007. After 11 pooled samples were made, concentrations of PCDD/Fs and dl-PCBs in breast milk pooled samples were measured by a high resolution gas chromatography - high resolution mass spectrometry (HRCG-HRMS) with isotope dilution.</p><p><b>RESULTS</b>For congeners of PCDD/Fs and dl-PCBs in human breast milk from Beijing, the highest content of congeners was octachlorodibenzo-p-dioxin (OCDD), polychlorinated biphenyl (PCB)-118, and PCB-105 with the median of 20.6 pg/g fat, 4.07 ng/g fat and 1.63 ng/g fat, respectively. The concentration median of total dioxins in 11 pooled human milk samples from Beijing was 7.4 pg TEQ/g fat. The highest was 13.5 pg TEQ/g fat from Tongzhou, and the lowest was 4.3 pg TEQ/g fat from Pinggu.</p><p><b>CONCLUSION</b>The contamination level of PCDD/Fs and dl-PCBs in human milk from Beijing is relatively low. However, with the rapid industrialization in China, the human body burden of PCDD/Fs and dl-PCBs will be likely to rise. Thus, further studies should be conducted to continuously monitor the trend of contamination level.</p>

Effects of Artemisia capillaris extract on disorders of hepatic functions and lipid metabolism in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) / 한국영양학회지

This study was conducted in order to investigate the effects of Artemisia capillaris (AC) extract on disorders of hepatic functions and lipid metabolism induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disrupter, using male rats (SD, five weeks old) for a period of three weeks. These 37 animals were divided into four groups. AC extract was added as 1.5% or 3% levels to basal diets, respectively. TCDD (40 ug/kg B.W) was administered by intraperitoneal injection into rats after a week from the beginning of the experiment. AC extract alleviated the increase of rat's relative liver weights induced by TCDD. Thymuses of all rats treated with TCDD were apparently shrunken by approximately 80%. Levels of white blood cells (WBC), red blood cells, hemoglobin, and hematocrits were significantly increased by treatment with TCDD, however, WBC tended to decrease by AC extract diets. In hepatic function, the elevation of glutamic oxalacetic transaminase activities by TCDD treatment was diminished by AC extract diets. Serum HDL-cholesterol levels were significantly elevated by AC extract diets. The apparent increase of triglyceride levels of rat livers induced by TCDD was significantly suppressed in the AC extract diet groups. Hepatic cytosolic catalase activities significantly decreased by treatment with TCDD showed a recovering trend by AC extract diets. In histochemical observation, the fat droplets and apoptosis of hepatocytes treated with TCDD were markedly alleviated by AC extract diets. These results indicated that AC could exert recovering effects on some disorders of hepatic functions, lipids metabolism, and antioxidant activities resulting from TCDD treatment.

Associations between Cigarette Smoking and Total Mortality Differ Depending on Serum Concentrations of Persistent Organic Pollutants among the Elderly

There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged > or = 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.

Associations between Cigarette Smoking and Total Mortality Differ Depending on Serum Concentrations of Persistent Organic Pollutants among the Elderly

There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged > or = 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.

The antagonistic effect of folic acid and resveratrol on cleft palate in mice induced by TCDD / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate whether or not administration of folic acid and resveratrol have preventive effects on cleft palate formation as well as the comparison of the two drugs' s effects.</p><p><b>METHODS</b>Pregnant mice were randomly divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28 microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13, followed hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group; resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same volume of water for 6 consecutive days from GD8 to GD13 and were given a single dose of corn oil on GD10. The pregnant mice weight and embryos, the number of live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by microscopy.</p><p><b>RESULTS</b>Total frequency of clefts was 92.86% in TCDD group, 84.00% (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD groups. The frequency of cleft was 0% in the control group. Compared with the control and the TCDD groups, there were significant differences in the number of live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P < 0.05). No significant differences in embryonic weight, live fetuses weight, the number of live, dead and resorption fetal mice were found in the other groups (P > 0.05).</p><p><b>CONCLUSION</b>Test dose of folic acid and resveratrol both had certain antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10 mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action. Effects of both the two drugs have no significant difference, but resveratrol (50 mg/kg, GD8-13) significantly affects the fetal mice's growth and development under TCDD exposure in utero.</p>