定量有害结局路径(qAOP)评估环境化学物质毒性的研究进展Ⅱ：类二噁英物质及AhR-qAOP
Research Advance of Quantitative Adverse Outcome Pathway (qAOP) in Environmental Chemicals Toxicity Assessment Ⅱ: Dioxin-like Compounds and AhR-qAOP
-
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。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.
-
-
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):37-51 Wei 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):1791-1796 Wei 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 -
点击查看大图
计量
- 文章访问数: 807
- HTML全文浏览数: 807
- PDF下载数: 78
- 施引文献: 0
下载:
