Toxic effects and mechanisms of exposure to single and mixture of mercury, cadmium, lead and arsenic
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摘要: 汞、镉、铅和砷是自然界中毒性较强的金属,镉和砷已确定为致癌物,汞和铅为可能致癌物。人类活动过程的排放是汞、镉、铅和砷的主要污染来源,由这些金属污染物暴露导致的人类疾病已经引起了公众的广泛关注。研究汞、镉、铅和砷在环境中实际暴露水平,尤其是汞、镉、铅和砷复合暴露对人体健康和生态环境影响及毒性效应的机理极为重要。根据暴露途径、暴露剂量和暴露时间,汞、镉、铅和砷具有不同的代谢途径,产生不同的毒性效应,具有不同的毒性效应机理。在总结现有汞、镉、铅、砷单一和混合暴露的健康损害及毒性效应的基础上,回顾、归纳汞、镉、铅和砷诱导产生毒性效应的机理,讨论基因组、转录组、蛋白质组和代谢组学等技术在汞、镉、铅和砷单一、混合毒性效应及机理研究中的应用并探讨 来的研究方向。Abstract: Metals including mercury, cadmium, lead and arsenic in nature are harmful to wildlife and humans. Cadmium and arsenic and/or their related compounds are well-known carcinogens, while mercury and lead may even cause cancer. Human activities are the main sources of mercury, cadmium, lead and arsenic contamination. A group of human diseases are suspected to result from exposure to these metals, and have awakened the public conscious to pay more attention to the risk of these metals in human health. Extensive studies have demonstrated the associations between adverse health effects and exposure to these metals at high dose. However, there is a paucity of information on the adverse effects associated with chronic exposure to the environmentally relevant levels of individual metals and mixtures. The impacts of exposure to mixtures of these metals on human health need to be examined. Depending on exposure route, dose and exposure duration, mercury, cadmium, lead and arsenic differ in metabolic fate, mechanisms of transport and disposition in the body, and have the individual toxicological profiles. The adverse effects and potential molecular evidences associated with the exposure to single and mixture of mercury, cadmium, lead and arsenic were summarized. The applications and future research directions of omics technology, such as genomics, transcriptomics, proteomics, and metabolomics in understanding the mechanisms related to toxicities were also discussed.
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[1] ZHANG L, WANG S X, WANG L , et al. Updated emission inventories for speciated atmospheric mercury from anthropogenic sources in China[J]. Environmental Science & Technology, 2015,49(5):3185-3194.
doi: 10.1021/es504840m pmid: 25655106[2] TIAN H Z, ZHU C Y, GAO J J , et al. Quantitative assessment of atmospheric emissions of toxic heavy metals from anthropogenic sources in China: historical trend,spatial variation distribution,uncertainties and control policies[J]. Atmospheric Chemistry & Physics, 2015,15(8):12107-12166.
doi: 10.5194/acp-15-10127-2015[3] WANG Y, CHENG K, WU W , et al. Atmospheric emissions of typical toxic heavy metals from open burning of municipal solid waste in China[J]. Atmospheric Environment,2016,152.10.1016/j.atmosenv. 2016. 12. 017.
doi: 10.1016/j.atmosenv.2016.12.017[4] TCHOUNWOU P B, YEDJOU C G, PATLOLLA A K , et al. Heavy metals toxicity and the environment[J]. Experientia Supplementum, 2012,101:133-164.
doi: 10.1007/978-3-7643-8340-4[5] JADHAV S H, SARKAR S N, TRIPATHIT H C . Cytogenetic effects of a mixture of selected metals following subchronic exposure through drinking water in male rats[J]. Indian Journal of Experimental Biology, 2006,44(12):997-1005.
pmid: 17176674[6] EKINO S, SUSA M, NINOMIYA T , et al. Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning[J]. Journal of the Neurological Sciences, 2007,262(1/2):131-144.
doi: 10.1016/j.jns.2007.06.036 pmid: 17681548[7] GENTÉS S, MAURYBRACHET R, FENG C , et al. Specific effects of dietary methylmercury and inorganic mercury in zebrafish (Danio rerio) determined by genetic,histological and metallothionein responses[J]. Environmental Science & Technology, 2015,49(24):14560-14569. [8] HO N Y, YANG L, LEGRADI J , et al. Gene responses in the central nervous system of zebrafish embryos exposed to the neurotoxicant methyl mercury[J]. Environmental Science & Technology, 2013,47(7):3316-3325.
doi: 10.1021/es3050967 pmid: 23458150[9] 王丽, 贾光, 闫蕾 , 等. 母鼠低剂量甲基汞染毒致亲、仔代肝脏的氧化损伤[J]. 环境与职业医学, 2005,22(6):495-497.
doi: 10.3969/j.issn.1006-3617.2005.06.004WANG L, JIA G, YAN L , et al. Effects of maternal exposure to low-level methylmercury on the growth of offspring and lipid peroxidation in liver[J]. Journal of Labour Medicine, 2005,22(6):495-497. doi: 10.3969/j.issn.1006-3617.2005.06.004[10] 陈敏, 谢吉民, 曹友清 , 等. 氯化汞对小鼠肾脏的急性毒性机制探讨[J]. 中国工业医学杂志, 2001,14(5):266-267.
doi: 10.3969/j.issn.1002-221X.2001.05.004CHEN M, XIE J M, CAO Y Q , et al. Studies on mechanism of acute renal toxicity of mercury chloride in mice[J]. Chinese Journal of Industrial Medicine, 2001,14(5):266-267. doi: 10.3969/j.issn.1002-221X.2001.05.004[11] 徐乐焱, 王毅, 邱炳源 , 等. 锌金属硫蛋白拮抗甲基汞对红细胞膜损伤的作用[J]. 卫生研究, 2000,29(2):80-82.
doi: 10.3969/j.issn.1000-8020.2000.02.007XU L Y, WANG Y, QIU B Y , et al. The protective effects of zinc metal lothionein against erythrocyte membrane damage induced by methylmercury[J]. Journal of Hygiene Research, 2000,29(2):80-82. doi: 10.3969/j.issn.1000-8020.2000.02.007[12] MINGHUA W, YUYU W, JUAN W , et al. Proteome profiles in medaka (Oryzias melastigma) liver and brain experimentally exposed to acute inorganic mercury[J]. Aquatic Toxicology, 2011,103(3/4):129-139.
doi: 10.1016/j.aquatox.2011.02.020 pmid: 21458406[13] WANG Y Y, WANG D Z, LIN L , et al. Quantitative proteomic analysis reveals proteins involved in the neurotoxicity of marine medaka Oryzias melastigma chronically exposed to inorganic mercury[J]. Chemosphere, 2015,119:1126-1133.
doi: 10.1016/j.chemosphere.2014.09.053 pmid: 25460752[14] ALEXANDER J, BENFORD D, COCKBUM A , et al. Scientific opinion of the panel on contaminants in the food chain on a request from the European Commission on cadmium in food[J]. Efsa Journal, 2009,7(3):1-139. [15] ÅKESSON A, PER B, THOMAS L , et al. Cadmium-induced effects on bone in a population-based study of women[J]. Environmental Health Perspectives, 2006,114(6):830-834.
doi: 10.1289/ehp.8763 pmid: 1480481[16] MADEJCZYK M S, BAER C E, DENNIS W E , et al. Temporal changes in rat liver gene expression after acute cadmium and chromium exposure[J]. Plos One, 2015,10(5):e0127327.
doi: 10.1371/journal.pone.0127327 pmid: 25993096[17] KAHKASHAN R, KRISHNENDU S, SIL P C . An update on oxidative stress-mediated organ pathophysiology[J]. Food & Chemical Toxicology An International Journal Published for the British Industrial Biological Research Association, 2013,62(12):584-600.
doi: 10.1016/j.fct.2013.09.026 pmid: 24084033[18] JIN T, WU X, TANG Y , et al. Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China[J]. Biometals An International Journal on the Role of Metal Ions in Biology Biochemistry & Medicine, 2004,17(5):525-530. [19] YANG J M, AMUSH M, CHEN Q Y , et al. Cadmium-induced damage to primary cultures of rat Leydig cells[J]. Reproductive Toxicology, 2003,17(5):553-560.
doi: 10.1016/S0890-6238(03)00100-X pmid: 14555193[20] OHTA H, CHERIAN M G . Gastrointestinal absorption of cadmium and metallothionein[J]. Toxicology & Applied Pharmacology, 1991,107(1):63-72.
doi: 10.1016/0041-008X(91)90331-8 pmid: 1987661[21] JOMOVA K, VALKO M . Advances in metal-induced oxidative stress and human disease[J]. Toxicology, 2011,283(2/3):65-87.
doi: 10.1016/j.tox.2011.03.001 pmid: 21414382[22] WÄTJEN W, BEYERSMANN D . Cadmium-induced apoptosis in C6 glioma cells: influence of oxidative stress[J]. Biometals, 2004,17(1):65-78.
doi: 10.1023/A:1024405119018 pmid: 14977363[23] KOEDRITH P, KIM H, WEON J I , et al. Toxicogenomic approaches for understanding molecular mechanisms of heavy metal mutagenicity and carcinogenicity[J]. International Journal of Hygiene & Environmental Health, 2013,216(5):587-598.
doi: 10.1016/j.ijheh.2013.02.010 pmid: 23540489[24] 徐进, 徐立红 . 环境铅污染及其毒性的研究进展[J]. 环境与职业医学, 2005,22(3):271-274.
doi: 10.3969/j.issn.1006-3617.2005.03.028XU J, XU L H . Environmental lead pollution and progress in the study of lead toxicity[J]. Journal of Labour Medicine, 2005,22(3):271-274. doi: 10.3969/j.issn.1006-3617.2005.03.028[25] LANDRIGAN P, NORDBERG M, LUCCHINI R , et al. The declaration of Brescia on prevention of the neurotoxicity of metals June 18,2006[J]. American Journal of Industrial Medicine, 2007,50(10):709.
doi: 10.1002/(ISSN)1097-0274[26] CANFIELD R L, JR H C, CORY-SLECHTA D A , et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter[J]. New England Journal of Medicine, 2003,348(16):1517-1526.
doi: 10.1056/NEJMoa022848[27] CHEN J, CHEN Y, WEI L , et al. Developmental lead acetate exposure induces embryonic toxicity and memory deficit in adult zebrafish[J]. Neurotoxicology & Teratology, 2012,34(6):581-586.
doi: 10.1016/j.ntt.2012.09.001 pmid: 22975620[28] LUO W, VERWEIJ R A, GESTEL C A M V . Determining the bioavailability and toxicity of lead contamination to earthworms requires using a combination of physicochemical and biological methods[J]. Environmental Pollution, 2014,185(1):1-9.
doi: 10.1016/j.envpol.2013.10.017 pmid: 24212065[29] 蒋晓红 . 铅的毒性和致癌性研究进展[J]. 职业卫生与应急救援, 2003,21(3):122-124.
doi: 10.3969/j.issn.1007-1326.2003.03.005JIANG X H . Progress study on toxicity and carcinogenicity of lead[J]. Occupational Health and Emergency Rescue, 2003,21(3):122-124. doi: 10.3969/j.issn.1007-1326.2003.03.005[30] SUSZKIW J B . Presynaptic disruption of transmitter release by lead[J]. Neurotoxicology, 2004,25(4):599-604.
doi: 10.1016/j.neuro.2003.09.009 pmid: 15183013[31] ERCAL N, GURERORHAN H, AYKINBURNS N . Toxic metals and oxidative stress: part Ⅰ. mechanisms involved in metal-induced oxidative damage[J]. Current Topics in Medicinal Chemistry, 2001,1(6):529-539.
doi: 10.2174/1568026013394831 pmid: 11895129[32] EUGENIO G, ANGELA A, RENATA P , et al. A proteomic approach to investigate the effects of cadmium and lead on human primary renal cells[J]. Metallomics, 2014,6(3):587-597.
doi: 10.1039/c3mt00344b pmid: 24419708[33] MUKHERJEE A, SENGUPTA M K, HOSSAIN M A , et al. Arsenic contamination in groundwater: a global perspective with emphasis on the Asian scenario[J]. Journal of Health, Population and Nutrition, 2006,24(2):142-163.
doi: 10.1029/2005JG000083 pmid: 17195556[34] GUPTA R, FLORA S J S .Effect of centella asiatica,on arsenic induced oxidative stress and metal distribution in rats[J]. Journal of Applied Toxicology Jat, 2006,26(3):213-222.
doi: 10.1002/jat.1131 pmid: 16389662[35] OLIVARES C I, FIELD J A, SIMONICH M , et al. Arsenic (Ⅲ,Ⅴ),indium (Ⅲ),and gallium (Ⅲ) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay[J]. Chemosphere, 2016,148:361-368.
doi: 10.1016/j.chemosphere.2016.01.050 pmid: 4754138[36] LU K, ABO R P, SCHLIEPER K A , et al. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis[J]. Environmental Health Perspectives, 2014,122(3):284-291.
doi: 10.1289/ehp.1307429 pmid: 3948040[37] HUGHES M F, BECK B D, CHEN Y , et al. Arsenic exposure and toxicology: a historical perspective[J]. Toxicological Sciences, 2011,123(2):305-332.
doi: 10.1093/toxsci/kfr184 pmid: 3179678[38] DELNOMDEDIEU M, BASTI M M, STYBLO M , et al. Complexation of arsenic species in rabbit erythrocytes[J]. Chemical Research in Toxicology, 1994,7(5):621-627.
doi: 10.1021/tx00041a006 pmid: 7841340[39] VALKO M, MORRIS H, CRONIN M T M , et al. Toxicity and oxidative stress[J]. Current Medicinal Chemistry, 2005,12(10):1161.
doi: 10.2174/0929867053764635[40] BRANDAO R, SANTOS F, ZENI G J , et al. DMPS and N-acetylcysteine induced renal toxicity in mice exposed to mercury[J]. Biometals, 2006,19(4):389-398.
doi: 10.1007/s10534-005-4020-3 pmid: 16841248[41] AGGARWAL M, WANGIKAR P B, SARKAR S N , et al. Effects of low-level arsenic exposure on the developmental toxicity of anilofos in rats[J]. Journal of Applied Toxicology, 2010,27(3):255-261.
doi: 10.1002/jat.1203 pmid: 17304642[42] CARVALHO C M, LU J, ZHANG X , et al. Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning[J]. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology, 2011,25(1):370-381.
doi: 10.1096/fj.10-157594 pmid: 20810785[43] YUAN G, DAI S, YIN Z , et al. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats[J]. Food & Chemical Toxicology, 2014,65(1):260-268.
doi: 10.1016/j.fct.2013.12.041 pmid: 24394482[44] 卢洪可, 戴书俊, 殷中琼 , 等. 实验性急性大鼠铅镉联合中毒对骨骼损伤的研究[J].中国兽医科学, 2012(12):1278-1282.LU H K, DAI S J, YIN Z Q , et al. Study on damage of bone in rat induced by experimental acute combined exposure to lead and cadmium[J].Chinese Veterinary Science, 2012(12):1278-1282. [45] FATHALLAH S, MEDHIOUB M N, KRAIEM M M . Combined toxicity of lead and cadmium on embryogenesis and early larval stages of the European clam ruditapes decussatus[J]. Environmental Engineering Science, 2013,30(7):357-364.
doi: 10.1089/ees.2012.0209[46] VELLINGER C, PARANT M, ROUSSELLE P , et al. Antagonistic toxicity of arsenate and cadmium in a freshwater amphipod (Gammarus pulex)[J]. Ecotoxicology, 2012,21(7):1817-1827.
doi: 10.1007/s10646-012-0916-1 pmid: 22535317[47] WHITTAKER M H, WANG G, CHEN X Q , et al. Exposure to Pb,Cd,and As mixtures potentiates the production of oxidative stress precursors: 30-day,90-day,and 180-day drinking water studies in rats[J]. Toxicology & Applied Pharmacology, 2011,254(2):154-166.
doi: 10.1016/j.taap.2010.10.025 pmid: 21034764[48] MARTíNEZ-PACHECO M, HIDALGO-MIRANDA A, ROMERO-CÓRDOBA S , et al. mRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects[J]. Gene, 2014,533(2):508-514.
doi: 10.1016/j.gene.2013.09.049 pmid: 24080485[49] MALMQUIST S J, ABRAMSSON A, MCGRAW H F , et al. Exposure to As,Cd and Pb-mixture impairs myelin and axon development in rat brain,optic nerve and retina[J]. Behaviour Research & Therapy, 2013,273(2):242-258.
doi: 10.1016/j.brat.2004.12.007 pmid: 16389061[50] COBBINA S J, CHEN Y, ZHOU Z , et al. Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals[J]. Journal of Hazardous Materials, 2015,294:109-120.
doi: 10.1016/j.jhazmat.2015.03.057 pmid: 25863025[51] COBBINA S J, XU H, ZHAO T , et al. A multivariate assessment of innate immune-related gene expressions due to exposure to low concentration individual and mixtures of four kinds of heavy metals on zebrafish (Danio rerio) embryos[J]. Fish & Shellfish Immunology, 2015,47(2):1032-1042.
doi: 10.1016/j.fsi.2015.11.003 pmid: 26549173[52] COBBINA S J, MAO G, ZHAO T , et al. Modulation of N -Methyl-D-aspartate receptors (NMDAR),Bcl-2 and c-fos gene expressions on exposure to individual and mixtures of low concentration metals in zebrafish (Danio rerio)[J]. Archives of Environmental Contamination & Toxicology, 2017,72(3):418-427. [53] JADHAV S H, SARKAR S N, PATIL R D , et al. Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: a biochemical and histopathological study in male rats[J]. Archives of Environmental Contamination & Toxicology, 2007,53(4):667-677.
doi: 10.1007/s00244-007-0031-0 pmid: 17882470[54] JADHAV S H, SARKAR S N, RAM G C , et al. Immunosuppressive effect of subchronic exposure to a mixture of eight heavy metals,found as groundwater contaminants in different areas of India,through drinking water in male rats[J]. Archives of Environmental Contamination & Toxicology, 2007,53(3):450-458.
doi: 10.1007/s00244-006-0177-1 pmid: 17657459[55] FOWLER B A, WHITTAKER M H, LIPSKY M , et al. Oxidative stress induced by lead,cadmium and arsenic mixtures: 30-day,90-day,and 180-day drinking water studies in rats: an overview[J]. Biometals, 2004,17(5):567-568.
doi: 10.1023/B:BIOM.0000045740.52182.9d pmid: 15688865[56] JADHAV S H, SARKAR S N, KATARIA M , et al. Subchronic exposure to a mixture of groundwater-contaminating metals through drinking water induces oxidative stress in male rats[J]. Environmental Toxicology & Pharmacology, 2007,23(2):205-211.
doi: 10.1016/j.etap.2006.09.004 pmid: 21783759[57] COBBINA S J, CHEN Y, ZHOU Z , et al. Low concentration toxic metal mixture interactions: effects on essential and non-essential metals in brain,liver,and kidneys of mice on sub-chronic exposure[J]. Chemosphere, 2015,132:79-86.
doi: 10.1016/j.chemosphere.2015.03.013 pmid: 25828250[58] LEONARD S S, HARRIS G K, SHI X . Metal-induced oxidative stress and signal transduction[J]. Free Radical Biology & Medicine, 2004,37(12):1921-1942.
doi: 10.1016/j.freeradbiomed.2004.09.010 pmid: 15544913[59] YANG L, KEMADJOU J R, ZINSMEISTER C , et al. Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo[J]. Genome Biology, 2007,8(10):1-17.
doi: 10.1186/gb-2007-8-10-r227 pmid: 2246301[60] MARSIT C J . Influence of environmental exposure on human epigenetic regulation[J]. Journal of Experimental Biology, 2015,218(1):71-79.
doi: 10.1242/jeb.106971 pmid: 25568453[61] CERNá M, KRSKOVá A, CEJCHANOVá M , et al. Human biomonitoring in the Czech Republic: an overview[J]. International Journal of Hygiene & Environmental Health, 2012,215(2):109-119.
doi: 10.1016/j.ijheh.2011.09.007 pmid: 22014893
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