彭颖1,2,,,
张睿3,
张瀚心4,
张效伟1,,
1. 污染控制与资源化研究国家重点实验室, 南京大学环境学院, 南京 210023;
2. 流域环境生态工程研发中心, 北京师范大学自然科学高等研究院, 珠海 519087;
3. 济南大学水利与环境学院, 济南 250022;
4. 生态环境部固体废物与化学品管理技术中心化学品部, 北京 100029
作者简介: 田明明(1994-),男,博士研究生,研究方向为环境功能基因组学,E-mail:tianzhuangm@126.com.
通讯作者: 彭颖,pengying2009@live.cn ; 张效伟,zhangxw@nju.edu.cn
基金项目: 国家重点研发计划课题（2018YFC1801606，2018YFC1801605）；国家自然科学基金资助项目（21707069，21806052）中图分类号: X171.5
Research Advance of Quantitative Adverse Outcome Pathway (qAOP) in Environmental Chemicals Toxicity Assessment Ⅱ: Dioxin-like Compounds and AhR-qAOP
Tian Mingming1,Peng Ying1,2,,,
Zhang Rui3,
Zhang Hanxin4,
Zhang Xiaowei1,,
1. State Key Laboratory of Pollution Control&Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China;
2. Research and Development Center for Watershed Environmental Eco-Engineering, Advanced Institute of Natural Sciences, Beijing Normal University, Zhuhai 519087, China;
3. School of Water Conservancy and Environment, University of Jinan, Jinan 250022, China;
4. Solid Waste and Chemicals Management Center, Ministry of Ecology and Environment, Beijing 100029, China
Corresponding authors: Peng Ying,pengying2009@live.cn ; Zhang Xiaowei,zhangxw@nju.edu.cn
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:环境中不断检出具有二噁英结构并存在潜在生物毒性的新型污染物类二噁英物质（dioxin-like compounds，DLCs），识别并评估其生态与人体毒性对化学品风险防控具有重要意义。传统的化学品毒性测试方法已不能满足评估大批环境化学物质风险的需求，基于芳香烃受体（aryl hydrocarbon receptor，AhR）的有害结局路径（adverse outcome pathway，AOP）为准确评估潜在DLCs的生态与健康风险提供了新的策略。为指导预测新型DLCs的毒性，需在定性AhR-AOP基础上发展定量AOP。本文综述了AhR-AOP的研究现状，并总结了“AhR激活-胚胎毒性”定量AOP的最新进展，包括定量模型的开发、相关体外测试技术、对新型DLCs和不同物种的危害评估的适用性等。最后探讨了AhR-qAOP发展过程中的问题与潜在解决方案，对其应用于DLCs生态危害与风险评价的前景进行了展望。
关键词: 类二噁英物质/
生态风险评估/
预测毒理学/
定量有害结局路径/
物种敏感性
Abstract:Emerging dioxin like compounds (DLCs) with the structure similar to dioxin and potential biological toxicity have been continuously detected in the environment. It is important to assess their ecological health risks for the management of chemical risk. Conventional approaches of toxic tests have failed to meet the demand of chemicals risk assessment. The adverse outcome pathways (AOPs) based on the aryl hydrocarbon receptor (AhR) provided a new strategy for accurately assessing the ecological health risks of potential DLCs, which can guide the toxicity prediction of emerging pollutants and the establishment of environmental benchmarks for the protection of ecological species. However, to achieve this goal, it is necessary to develop quantitative AOP on the basis of the improvement and development of qualitative AhR-AOP. This paper reviewed the research advance of AhR-AOP, and summarized the latest development of the quantitative AOP (qAOP) based on embryo mortality owning to AhR activation, including the development of quantitative models, the in vitro bioassay technology, as well as the applicability for diverse species in hazard assessment of emerging DLCs. Finally, the most important issues and potential solutions in the development of AhR-qAOP were discussed, and its application in the assessment of ecological hazard and ecological risks of DLCs was prospected in this review.
Key words:dioxin-liked compounds/
ecological risk assessment/
predictive toxicology/
quantitative adverse outcome pathway/
species sensitivity.
| Moura-Alves P, Faé K, Houthuys E, et al. AhR sensing of bacterial pigments regulates antibacterial defence[J]. Nature, 2014, 512(7515):387-392 |
| 魏凤华, 张俊江, 夏普, 等. 类二噁英物质及芳香烃受体(AhR)介导的有害结局路径(AOP)研究进展[J]. 生态毒理学报, 2016, 11(1):37-51Wei F H, Zhang J J, Xia P, et al. Research progress on dioxin-like compounds and AhR-mediated adverse outcome pathway (AOP)[J]. Asian Journal of Ecotoxicology, 2016, 11(1):37-51(in Chinese) |
| Kennedy G D, Nukaya M, Moran S M, et al. Liver tumor promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin is dependent on the aryl hydrocarbon receptor and TNF/IL-1 receptors[J]. Toxicological Sciences, 2014, 140(1):135-143 |
| Perkins E J, Ashauer R, Burgoon L, et al. Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment[J]. Environmental Toxicology and Chemistry, 2019, 38(9):1850-1865 |
| Pavek P, Dvorak Z. Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues[J]. Current Drug Metabolism, 2008, 9(2):129-143 |
| Fujii-Kuriyama Y, Kawajiri K. Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli[J]. Proceedings of the Japan Academy Series B, Physical and Biological Sciences, 2010, 86(1):40-53 |
| Hahn M E. Aryl hydrocarbon receptors:Diversity and evolution[J]. Chemico-Biological Interactions, 2002, 141(1-2):131-160 |
| Karchner S I, Franks D G, Powell W H, et al. Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family:AHR repressor, AHR1, and AHR2[J]. The Journal of Biological Chemistry, 2002, 277(9):6949-6959 |
| Koh D H, Hwang J H, Park J G, et al. The AHR1-ARNT1 dimerization pair is a major regulator of the response to natural ligands, but not to TCDD, in the chicken[J]. Ecotoxicology and Environmental Safety, 2020, 201:110835 |
| Doering J A, Giesy J P, Wiseman S, et al. Predicting the sensitivity of fishes to dioxin-like compounds:Possible role of the aryl hydrocarbon receptor (AhR) ligand binding domain[J]. Environmental Science and Pollution Research International, 2013, 20(3):1219-1224 |
| Hahn M E. Dioxin toxicology and the aryl hydrocarbon receptor:Insights from fish and other non-traditional models[J]. Marine Biotechnology, 2001, 3(Suppl.1):S224-S238 |
| Zhang S K, Peng P G, Huang W L, et al. PCDD/PCDF pollution in soils and sediments from the Pearl River Delta of China[J]. Chemosphere, 2009, 75(9):1186-1195 |
| Zhang T, Chen S, Li N, et al. Occurrence, sources and ecological risks of PCDD/Fs and DL-PCBs in surface sediments from rivers in city cluster in south Jiangsu Province, China[J]. Environmental Chemistry, 2014, 33(9):1445-1455 |
| Klinčić D, Dvoršćak M, Jagić K, et al. Levels and distribution of polybrominated diphenyl ethers in humans and environmental compartments:A comprehensive review of the last five years of research[J]. Environmental Science and Pollution Research International, 2020, 27(6):5744-5758 |
| Kanaya N, Bernal L, Chang G, et al. Molecular mechanisms of polybrominated diphenyl ethers (BDE-47, BDE-100, and BDE-153) in human breast cancer cells and patient-derived xenografts[J]. Toxicological Sciences, 2019, 169(2):380-398 |
| Zhang L, Jin Y R, Han Z H, et al. Integrated in silico and in vivo approaches to investigate effects of BDE-99 mediated by the nuclear receptors on developing zebrafish[J]. Environmental Toxicology and Chemistry, 2018, 37(3):780-787 |
| Zhang R, Zhang X W, Zhang J J, et al. Activation of avian aryl hydrocarbon receptor and inter-species sensitivity variations by polychlorinated diphenylsulfides[J]. Environmental Science & Technology, 2014, 48(18):10948-10956 |
| Zhang J J, Zhang X W, Xia P, et al. Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides[J]. Chemosphere, 2016, 144:1754-1762 |
| Ankley G T, Bennett R S, Erickson R J, et al. Adverse outcome pathways:A conceptual framework to support ecotoxicology research and risk assessment[J]. Environmental Toxicology and Chemistry, 2010, 29(3):730-741 |
| Hecker M, LaLone C A. Adverse outcome pathways:Moving from a scientific concept to an internationally accepted framework[J]. Environmental Toxicology and Chemistry, 2019, 38(6):1152-1163 |
| Poland A, Knutson J C. 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons:Examination of the mechanism of toxicity[J]. Annual Review of Pharmacology and Toxicology, 1982, 22:517-554 |
| Conolly R B, Ankley G T, Cheng W Y, et al. Quantitative adverse outcome pathways and their application to predictive toxicology[J]. Environmental Science & Technology, 2017, 51(8):4661-4672 |
| Pittman M E, Edwards S W, Ives C, et al. AOP-DB:A database resource for the exploration of adverse outcome pathways through integrated association networks[J]. Toxicology and Applied Pharmacology, 2018, 343:71-83 |
| Teraoka H, Okuno Y, Nijoukubo D, et al. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish[J]. Aquatic Toxicology, 2014, 154:19-26 |
| Lanham K A, Plavicki J, Peterson R E, et al. Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish[J]. Toxicological Sciences, 2014, 141(1):141-154 |
| Smith A G, Clothier B, Carthew P, et al. Protection of the Cyp1a2(-/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Toxicology and Applied Pharmacology, 2001, 173(2):89-98 |
| Doering J A, Wiseman S, Giesy J P, et al. A cross-species quantitative adverse outcome pathway for activation of the aryl hydrocarbon receptor leading to early life stage mortality in birds and fishes[J]. Environmental Science & Technology, 2018, 52(13):7524-7533 |
| Kim Y, Cooper K R. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) in the embryos and newly hatched larvae of the Japanese medaka (Oryzias latipes)[J]. Chemosphere, 1999, 39(3):527-538 |
| Handel C M, van Hemert C. Environmental contaminants and chromosomal damage associated with beak deformities in a resident North American passerine[J]. Environmental Toxicology and Chemistry, 2015, 34(2):314-327 |
| Mylchreest E, Charbonneau M. Studies on the mechanism of uroporphyrinogen decarboxylase inhibition in hexachlorobenzene-induced Porphyria in the female rat[J]. Toxicology and Applied Pharmacology, 1997, 145(1):23-33 |
| James C A, Marks G S. Inhibition of chick embryo hepatic uroporphyrinogen decarboxylase by components of xenobiotic-treated chick embryo hepatocytes in culture[J]. Canadian Journal of Physiology and Pharmacology, 1989, 67(3):246-249 |
| Doering J A, Wiseman S, Beitel S C, et al. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds[J]. Aquatic Toxicology, 2014, 150:27-35 |
| Zhang R, Manning G E, Farmahin R, et al. Relative potencies of aroclor mixtures derived from avian in vitro bioassays:Comparisons with calculated toxic equivalents[J]. Environmental Science & Technology, 2013, 47(15):8852-8861 |
| Mandavia C. TCDD-induced activation of aryl hydrocarbon receptor regulates the skin stem cell population[J]. Medical Hypotheses, 2015, 84(3):204-208 |
| 魏凤华, 张效伟, 张睿, 等. 鸟类AhR报告基因法对垃圾焚烧炉飞灰中的类二噁英污染物的评估[J]. 中国科技论文, 2016, 11(15):1791-1796Wei F H, Zhang X W, Zhang R, et al. Assessment of the dioxin-like compounds in fly ash of the waste incinerator by avian AhR luciferase report gene assay[J]. China Sciencepaper, 2016, 11(15):1791-1796(in Chinese) |
| 夏洁. 二恶英类污染物的高通量生物检测技术研究及其在环境监测中的应用[D]. 南京:南京大学, 2013:21-31 Xia J. Development of a high throughput bio-analytical method of dioxin-like compounds and its application in environmental monitoring[D]. Nanjing:Nanjing University, 2013:21-31(in Chinese) |
| Mundy L J, Williams K L, Chiu S, et al. Extracts of passive samplers deployed in variably contaminated wetlands in the athabasca oil sands region elicit biochemical and transcriptomic effects in avian hepatocytes[J]. Environmental Science & Technology, 2019, 53(15):9192-9202 |
| Doering J A, Dubiel J, Wiseman S. Predicting early life stage mortality in birds and fishes from exposure to low-potency agonists of the aryl hydrocarbon receptor:A cross-species quantitative adverse outcome pathway approach[J]. Environmental Toxicology and Chemistry, 2020, 39(10):2055-2064 |
| Manning G E, Farmahin R, Crump D, et al. A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD50 of polychlorinated biphenyls in avian species[J]. Toxicology and Applied Pharmacology, 2012, 263(3):390-401 |
| Manning G E, Mundy L J, Crump D, et al. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls:Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity[J]. Toxicology and Applied Pharmacology, 2013, 266(1):38-47 |
| Peng Y, Xia P, Zhang J J, et al. Toxicogenomic assessment of 6-OH-BDE47-induced developmental toxicity in chicken embryos[J]. Environmental Science & Technology, 2016, 50(22):12493-12503 |
| Farmahin R, Wu D M, Crump D, et al. Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins[J]. Environmental Science & Technology, 2012, 46(5):2967-2975 |
| Farmahin R, Manning G E, Crump D, et al. Amino acid sequence of the ligand-binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin-like compounds[J]. Toxicological Sciences, 2013, 131(1):139-152 |
| Karchner S I, Franks D G, Kennedy S W, et al. The molecular basis for differential dioxin sensitivity in birds:Role of the aryl hydrocarbon receptor[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(16):6252-6257 |
| Cohen-Barnhouse A M, Zwiernik M J, Link J E, et al. Sensitivity of Japanese quail (Coturnix japonica), Common pheasant (Phasianus colchicus), and White leghorn chicken (Gallus gallus domesticus) embryos to in ovo exposure to TCDD, PeCDF, and TCDF[J]. Toxicological Sciences, 2011, 119(1):93-103 |
| Head J A, Hahn M E, Kennedy S W. Key amino acids in the aryl hydrocarbon receptor predict dioxin sensitivity in avian species[J]. Environmental Science & Technology, 2008, 42(19):7535-7541 |
| Goryo K, Suzuki A, Carpio C A D, et al. Identification of amino acid residues in the Ah receptor involved in ligand binding[J]. Biochemical and Biophysical Research Communications, 2007, 354(2):396-402 |
| Ema M, Ohe N, Suzuki M, et al. Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors[J]. The Journal of Biological Chemistry, 1994, 269(44):27337-27343 |
| Pandini A, Denison M S, Song Y J, et al. Structural and functional characterization of the aryl hydrocarbon receptor ligand binding domain by homology modeling and mutational analysis[J]. Biochemistry, 2007, 46(3):696-708 |
| Abnet C C, Tanguay R L, Hahn M E, et al. Two forms of aryl hydrocarbon receptor type 2 in rainbow trout (Oncorhynchus mykiss):Evidence for differential expression and enhancer specificity[J]. Journal of Biological Chemistry, 1999, 274(21):15159-15166 |
| Zhang R, Wang X X, Zhang X S, et al. Polychlorinated diphenylsulfides activate aryl hydrocarbon receptor 2 in zebrafish embryos:Potential mechanism of developmental toxicity[J]. Environmental Science & Technology, 2018, 52(7):4402-4412 |
| White D H, Hoffman D J. Effects of polychlorinated dibenzo-p-dioxins and dibenzofurans on nesting wood ducks (Aix sponsa) at Bayou Meto, Arkansas[J]. Environmental Health Perspectives, 1995, 103(Suppl.4):37-39 |
| Fujisawa N, Nakayama S M M, Ikenaka Y, et al. TCDD-induced chick cardiotoxicity is abolished by a selective cyclooxygenase-2(COX-2) inhibitor NS398[J]. Archives of Toxicology, 2014, 88(9):1739-1748 |
| Dong W, Matsumura F, Kullman S W. TCDD induced pericardial edema and relative COX-2 expression in medaka (Oryzias latipes) embryos[J]. Toxicological Sciences, 2010, 118(1):213-223 |
| Doering J A, Farmahin R, Wiseman S, et al. Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain[J]. Environmental Science & Technology, 2015, 49(7):4681-4689 |
| Tillitt D E, Buckler J A, Nicks D K, et al. Sensitivity of lake sturgeon (Acipenser fulvescens) early life stages to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,3',4,4',5-pentachlorobiphenyl[J]. Environmental Toxicology and Chemistry, 2017, 36(4):988-998 |
| Gunnarsson L, Jauhiainen A, Kristiansson E, et al. Evolutionary conservation of human drug targets in organisms used for environmental risk assessments[J]. Environmental Science & Technology, 2008, 42(15):5807-5813 |
| LaLone C A, Villeneuve D L, Lyons D, et al. Editor's highlight:Sequence alignment to predict across species susceptibility (SeqAPASS):A web-based tool for addressing the challenges of cross-species extrapolation of chemical toxicity[J]. Toxicological Sciences, 2016, 153(2):228-245 |
| Zhang R, Zhang J J, Zhang X W, et al. In vitro dioxin-like potencies of HO-and MeO-PBDEs and inter-species sensitivity variation in birds[J]. Ecotoxicology and Environmental Safety, 2016, 126:202-210 |
| Walker M K, Cook P M, Butterworth B C, et al. Potency of a complex mixture of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin in causing fish early life stage mortality[J]. Fundamental and Applied Toxicology:Official Journal of the Society of Toxicology, 1996, 30(2):178-186 |
| Wei F H, Li J Y, Zhang R, et al. Relative sensitivities among avian species to individual and mixtures of aryl hydrocarbon receptor-active compounds[J]. Environmental Toxicology and Chemistry, 2016, 35(5):1239-1246 |
| Patlewicz G, Simon T W, Rowlands J C, et al. Proposing a scientific confidence framework to help support the application of adverse outcome pathways for regulatory purposes[J]. Regulatory Toxicology and Pharmacology, 2015, 71(3):463-477 |
