Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria. It is the most toxic of the microcystins.
Structure
Microcystins are cyclic heptapeptides. The seven amino acids that are involved in the structure of a microcystin include the unique amino acids ADDA and D-β-methyl-isoaspartate (D-β-Me-isoAsp). Furthermore, microcystins contain two variable residues, which make the differentiation between variants of microcystins. These two variable functionalities are always standard proteinogenic amino acids - In microcystin-LR these are leucine and arginine.
The chemical composition of microcystin-LR, id made up of 7 amino acids
More than 250 microcystins have been identified to date,[1] representing differences in the two variable residues and some modifications in the other amino acids. These modifications include demethylation of Masp and Mdha and methylesterification of D-Glu. Different microcystins have different toxicity profiles, with microcystin-LR found to be the most toxic.[2][3]
Biosynthesis
Microcystins are small nonribosomal peptides. In Microcystis aeruginosa microcystin-LR is synthesized by proteins that encoded by a 55 kb microcystin-gene cluster (mcy) that contains 6 large (over 3 kb) genes that encode proteins with polyketide synthase activity, nonribosomal peptide synthase activity (mcyA-E and G) and 4 smaller genes (mcyF and H-J). These large proteins are made up of different protein domains, coined 'modules', that each have their own specific enzymatic function.[4]
Although the enzyme systems involved in the biosynthesis of microcystins is not identical among all cyanobacteria, there are large similarities and most of the essential enzymes are conserved.[4][5]
The biosynthesis of microcystin-LR in Microcystis aeruginosa begins with the coupling of phenylacetate to the mcyG enzyme. In a series of reactions, catalysed by different enzyme modules as well as different enzymes, microcystin-LR is formed. The entire biosynthesis pathway of microcystin-LR in Microcystis aeruginosa is illustrated in the figure.
The biosynthesis of microcystin-LR by Microcystis aeruginosa.
The first steps of the synthesis involve the insertion of several carbon- and oxygen atoms between the acetyl- and phenylgroup. This part of the synthesis is catalyzed by enzyme domains that possess β-ketoacylsynthase, acyltransferase, C-methyltransferase and ketoacyl reductase activity. At the end of this stage, that is, after the first condensation of glutamate, the amino acid Adda is formed.[4]
The second part of the synthesis involves the condensation of the amino acids of which the microcystin is composed. Thus, in the case of microcystin-LR the consecutive condensation of the amino acids glutamic acid, methyldehydroalanine, alanine, leucine, methylaspartic acid and arginine leads to the coupled product. A nucleophilic attack of the nitrogen in the Adda residue results in the release of the cyclic microcystin-LR.[4]
The different microcystins are all synthesized by the same[clarification needed] enzymes as microcystin-LR.[6]
Mechanism of toxicity
Microcystin-LR inhibits protein phosphatase type 1 and type 2A (PP1 and PP2A) activities in the cytoplasm of liver cells. This leads to an increase in phosphorylation of proteins in liver cells. The interaction of microcystin-LR to the phosphatases includes the formation of a covalent bond between a methylene group of microcystin-LR and a cystine residue at the catalytic subunit of the phosphoprotein phosphatase (PPP) family of serine/threonine-specific phosphatases, like PP1 and PP2A. When microcystin-LR binds directly to the catalytic center of the PPP enzymes, they block the access of the substrate to the active site completely and inhibition of the enzyme takes place. In this way the protein phosphatase is inhibited and more phosphorylated proteins in the liver cells are left, which is responsible for the hepatotoxicity of microcystin-LR.
The active site of catalytic PPP enzymes represents three surface grooves: the hydrophobic groove, the acidic groove and the C-terminal groove, which are Y-shaped with the active site at the bifurcation point. The Adda side-chain of microcystin-LR is accommodated to the hydrophobic groove, the carboxylic D-Glu site makes hydrogen bonds to metal-bound water molecules and the carboxyl group of the Masp site makes hydrogen bonds to conserved arginine and tyrosine residues in the PPP enzyme. Finally the methylene group at the Mdha site of microcystin-LR binds covalently to a S-atom of a cysteine residue, and the leucine residue packs closely to another conserved tyrosine residue.[2]
Effects
Microcystin-LR is toxic for both humans and animals. There are epidemiological results from studies that have shown symptoms of poisoning attributed to the presence of cyanotoxins in drinking water. The effects are divided in short-term and long-term effects.
Human poisonings
There are no verifiable reports of human deaths known to have been specifically caused by microcystin-LR, although there are reports of health effects after exposure and there have been deaths attributed to microcystins in general.[7] One of the most outstanding reports was an outbreak in Caruaru, Brazil, in 1996. 116 patients experienced multiple effects: visual disturbance, nausea, vomiting and muscle weakness. One hundred developed acute liver failure and 52 suffered from symptoms of what is now called "Caruaru Syndrome."[8] The syndrome was caused by dialysis therapy with water that had not been properly treated.[9]
Short-term effects
There are few short-term effects caused by exposure to microcystin-LR. Microcystins are primarily hepatotoxic compounds; therefore, noticeable toxic effects are not immediate. Most of the toxicity studies have been done with mice that received intra-peritoneal injections. The most common effect is liver damage,[10] Two of the most commonly seen symptoms are gastroenteritis and cholestatic liver disease.
In an experiment with mice, the animals died within a few hours after injection of a lethal dose of micocystin-LR. Liver damage could be noticed in 20 minutes. Within a few hours, liver cells died.[11]
Long-term effects
Acute microcystin-LR intoxication may result in long-term injury, while chronic low-level exposure may cause adverse health effects. From animal studies, it is proven that there will be chronic liver injury from oral exposure to microcystin-LR. It might even be carcinogenic. Cancers have been found during animal studies. Microcystin-LR itself does not cause cancer, but it may stimulate the growth of cancer cells.
Animal effects
Microcystin-LR had effects on all animals, not only the domestic animals from swimming in a river of drinking water with cyanobacteria blooms. Symptoms in domestic animal poisoning include diarrhea, vomiting, weakness, recumbency and are fatal in most cases[12][13]
Mircocystin-LR is toxic for all animals, including the animals consumed by humans. Fishes and birds are also at risk for microcystin-LR poisoning.
Exposure Routes
Cyanobacteria prefer to live in water bodies such as lake, ponds, reservoirs, and slow-moving streams. When the water is warm there are enough nutrients available for the bacteria to survive. Most cyanobacteria produce toxins, of which microcystin is only one group. When a cyanobacterium dies, its cell wall degrades while the toxins are released in the water. Microcystins are extremely stable in water and withstand chemical breakdown such as hydrolysis or oxidation. The half-life of this toxin is 3 weeks at pH 1 and 40 °C. At typical conditions in the environment, however, the half-life is 10 weeks.[10] Microcystin-LR water contamination is resistant to boiling and microwave treatments.[14]
After release in the water, microcystins are actively absorbed by fish and birds from intoxicated water and thus enter the food chain. Humans are also exposed to microcystins by performing activities in intoxicated water.[15]
Disposition and metabolism
Disposition
Microcystin-LR is rapidly excreted from the blood plasma. Plasma half-lives for the α- and β-stages, corresponding to distribution and elimination, are respectively 0.8 and 6.9 minutes.[16][17] The total clearance of the compound from the plasma is about 0.9 mL/min.
The excretion of the compound takes primarily place via the feces and urine. After 6 days approximately 24% of the intake is excreted from the body, of which about 9% is excreted via the feces and 14.5% via the urine.[17]
Microcystin-LR is mostly concentrated in the liver. Other tissues get exposed at much lower levels.[17]
Metabolism
Data about the metabolism of microcystin-LR in humans is very scarce. Data about metabolism and disposition of the toxin in mice and rats is more widely available. In these animals microcystin-LR is rapidly concentrated in the liver.[18] Intoxication of mice with microcystin-LR led to a decrease in the levels of cytochrome P450 and cytochrome b5 and an increase in cytochrome P420, to which CYP450 is converted. Together with the fact that mice with an induced higher concentration CYP450 are less affected by the toxin, this suggest that CYP450 plays an important role in the detoxification of the compound.
In phase 2 of the biotransformation the compound is conjugated with several different endogenous substances. Microcystin-LR is known to be excreted as glutathione conjugate, cysteine conjugate and an oxidized ADDA diene conjugate. The glutathione and cysteine conjugate with the Mda-moiety. The oxidized ADDA is conjugated at the conjugated bond.[19]
Many studies took place with intraperitoneal administration. Because of the differences in lipophilicity and polarity between the different microcystins, it cannot be presumed that the i.p. LD50 will predict toxicity after oral administration.[10]
Microcystins are hepatotoxins. After acute exposure, severe liver damage is noticeable by a disruption of liver cell structure. The liver weight will increase due to intrahepatic hemorrhage, haemodynamic shock, heart failure and death.[10]
After nasal administration of microcystin-LR, the epithelium of nasal mucosa of both the olfactory and respiratory zones were suffering from necrosis. Even liver lesions were noticed after oral administration. The LD50 for nasal administration is equal to the intraperitoneal administration.
Repeated oral administration
For the assessment of possible chronic human health effects, studies involving repeated oral administration of pure microcystins at various dose levels are most desirable.
In a mice study, pure mirocystin-LR was administered orally at doses 0, 40, 200 or 1000 μg/kg bodyweight. At the highest dose, almost all mice showed liver changes and chronic inflammation and a few other symptoms. In female mice only changes in transaminases were observed at the highest dose.[10]
Carcinogenicity
Microcystin alone
Mice showed neoplastic liver nodules after 100 oral administrations at 20 μg/kg bodyweight. The nodules observed were up to 5mm in diameter. However, no mice showed liver nodules after 100 administrations of 80 μg/kg.
Interaction with tumors
The IARC committee concluded that microcystin-LR is possibly carcinogenic to humans. So, microcystin-LR itself is not a carcinogen, but it stimulates tumor growth. Mice treated with the carcinogenic compound dimethylbenzathracene showed an increased number and weight of skin tumors.[7]
In vivo animal experiments
There is very little known about acute toxicity for humans, but there have been animal studies, showing the following results.
When microcystins are injected intravenously or intraperitoneally, they localize in the liver. This appears to be the result of uptake by hepatocytes. The WHO report states that microcystins are lethal to mice when they are exposed intraperitoneally to 25 to 150 μg/kg body weight.[10] Perhaps due to poor absorption after exposure, orally administered microscytins are less toxic, as a lethal dose in mice is about 5 to 10 μg/kg body weight. Hepatotoxicity in the form of hepatic necrosis occurs within 60 minutes after an intraveneous dose.[20]
Blooms of Microcystis aeruginosa did not cause increased tumor rates in groups of mice treated for up to one year. It is shown that mice given 20 μg/kg body weight 4 times a week during a period of 28 weeks developed neoplasms of the liver.[20] There results are, however, ambiguous.
By the oral route, microcystin-LR displays acute toxicity in rodents. It is apparent that a significant amount of the oral dose passes the intestinal barrier.
Developmental effects
Microcystins do not appear to show developmental toxicity.
Genotoxicity
The WHO states microcystin-LR has no mutagenic effect. However, the induction of DNA strand-breaks in lymphocytes has been observed in mice after single oral administration. The effect is time- and dose-dependent. There is no change in the expression of selected genes involved in the cellular response to DNA damage after a 4-hour exposure. After 24 hours, the DNA damage-responsive genes were upregulated, which indicates that microcystin-LR is an indirect genotoxic agent.[22]
In China, the highest incidence of liver cancer occurs in areas with abundant cyanobacteria in the surface waters. Tumor development is associated with low-concentration exposure over a long period of time.[20]
A metalloprotease enzyme isolated from bacteria at Lake Rotorua, among other locations, is called microcystinase. This particular enzyme turns microcystins into products with a 160-fold decrease in toxicity.[23]
History
The Chinese general Zhu-Ge Liang was the first to observe cyanobacteria poisoning about 1000 years ago. He reported the death of troops who drank green coloured water from a river in southern China.[citation needed] The first published report of an incidence of cyanobacteria poisoning dates from the poisoning of an Australian lake in 1878.[24] Also, in China and Brasil, people died after drinking water from a lake. All these incidents have been attributed to cyanobacteria and the toxic compound microcystin-LR. That is the reason why the World Health Organization (WHO) issued a guideline for microcystins in drinking water. The WHO guideline for microcystins in drinking water, based on microcystin-LR, is 1 μg/L.[16] With the high levels of Eutrophication in South Africa, typical exposures can be as high as 10 μg/L.[25][26][27][28]
References
^Structural Diversity, Characterization and Toxicology of Microcystins, doi: 10.3390/toxins11120714
^ abS. Pereira, V. Vasconcelos & A. Antunes, Computational study of the covalent bonding of microcystins to cysteine residues - a reaction involved in the inhibition of the PPP family of protein phosphatases, FEBS Journal, doi: 10.1111/j.1742-4658.2011.08454.x
^A. Campos & V. Vasconcelos, Molecular Mechanisms of Microcystin Toxicity in Animal Cells, Int. J. Mol. Sc., 11(1), pp. 268-287
^ abcdD. Tillett et al., Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system, Chem. Biol., 7(10), pp. 753-764
^G. Christiansen et al., Microcystin Biosynthesis in Planktothrix: Genes, Evolution, and Manipulation, J. Bacteriol., 185(2), pp. 564-572
^T. Nishizawa et al., Polyketide Synthase Gene Coupled to the Peptide Synthetase Module Involved in the Biosynthesis of the Cyclic Heptapeptide Microcystin, J. Biochem., 127(5), pp.779-789
^ abBulter, N., Carlisle, J.C. Microcystins: A brief overview of their toxicity and effects, with special reference to fish, wildlife and livestock. Department of Water Resources, California. January 2009.
^Azevedo, S.M. et al., Human intoxication by microcystins during renal dialysis treatment in Caruaru-Brazil. Toxicology, 2002. 181-182: p. 441-6.
^Jochimsen, E.M. et al., Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med, 1998. 338(13): p. 873-8.
^ abcdefWHO (2003) Cyanobacterial toxins: Microcystin-LR in drinking-water. Background document for preparation of WHO Guidelines for drinking-water quality. Geneva, World Health Organization WHO/SDE/WSH/03.04/57).
^Slatkin, D.N., et al., Atypical pulmonary thrombosis caused by a toxic cyanobacterial peptide. Science, 1983. 220(4604): p. 1383-5.
^DeVries, S.E., et al., Clinical and pathologic findings of blue-green algae (Microcystis aeruginosa) intoxication in a dog. Journal of Veterinary Diagnostic Investigation, 1993. 5(3): p. 403.
^Briand, J.F., et al., Health hazards for terrestrial vertebrates from toxic cyanobacteria in surface water ecosystems. Vet Res, 2003. 34(4): p. 361-77.
^Harada, K.I., et al., Stability of microcystins from cyanobacteria. III. Effect of pH and temperature Phycologia, 1996. 35(6) pp. 83-88
^ abChorus, I., and J. Bartram, Toxic cyanobacteria in water; A guide to their public health consequences, monitoring and management. London: E & FN Spon,1999.
^ abcRobinson, N.A., Pace, J.G., Matson, C.F., Miura, G.A. and Lawrence, W.B. 1991 Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice, J.Pharmacol. Exp. Ther., 256(1), 176-182.
^Brooks, W.P. and Codd, G.A. 1987 Distribution of Microcystis aeruginosa peptide toxin and interactions with hepatic microsomes in mice Pharmacol. Toxicol., 60(3), 187-191.
^Kondo, F., Matsumoto, H., Yamada, S., Ishikawa, N., Ito, E., Nagata, S., Ueno, Y., Suzuki, M. and Harada, K.-I. 1996 Detection and identification of metabolites of microcystins formed in vivo in mouse and rat livers Chem. Res. Toxicol., 9(8), 1355-1359.
^Francis, G. Poisonous Australian lake Nature 18, 11-12 (1878)
^Oberholster, P.J., Cloete, T.E., van Ginkel, C., Botha, A-M. & Ashton, P.J. 2008. The use of remote sensing and molecular markers as early warning indicators of the development of cyanobacterial hyperscum crust and microcystin-producing genotypes in the hypertrophic Lake Hartebeespoort, South Africa. Pretoria: Council for Scientific and Industrial Research (CSIR).
^Matthews, M.W., & Barnard, S. 2015. Eutrophication and Cyanobacteria in South Africa's Standing Water Bodies: A View from Space. In South African Journal of Science. Vol. 111. No. 5/6.
A bust of Alexander the Great Alexander the Great, a Dramatic Poem is a work by Irish poet and playwright Aubrey Thomas de Vere. It was published in 1874 by Henry S. King and Co. It tells about Macedonian king Alexander the Great and his war against the Persians. The drama was dedicated To the Memory of Coleridge. It is written in blank verse. There are more than 30 dramatis personae, to say nothing of anonymous soldiers and messengers.[1] According to the authors of the 1911 Encyclop...
Public health conditions related to clean water and proper excreta and sewage disposal Not to be confused with Sanitization. The sanitation system: collection, transport, treatment, disposal or reuse. Part of a series onPublic health Outline Subfields Community health Dental public health Environmental health Epidemiology Health economics Health education Health promotion Health policy Health politics Mental health Occupational safety Rehabilitation (penology) Sexual and reproductive health S...
Artikel ini sebatang kara, artinya tidak ada artikel lain yang memiliki pranala balik ke halaman ini.Bantulah menambah pranala ke artikel ini dari artikel yang berhubungan atau coba peralatan pencari pranala.Tag ini diberikan pada Februari 2023. Teknik telegraf adalah teknik yang mempelajari bagaimana cara kerja suatu telegraf yaitu suatu mesin atau alat yang dapat mengirim dan menerima pesan jarak jauh dalam bentuk kode. Garis Besar Ilmu Telegrap Ilmu Telegrap adalah salah satu metode Teleko...
INS Teg at sea History India NameINS Teg NamesakeSaber Ordered14 July 2007[1] BuilderYantar Shipyard Laid downJuly 2007 Launched27 November 2009 Acquired1 September 2011 Commissioned27 April 2012 MottoTowards Eternal Glory[2] Statusin active service General characteristics Class and typeTalwar-class frigate Displacement 3,620 long tons (3,678 t) standard 4,035 long tons (4,100 t) full load Length124.8 m (409 ft 5 in) Beam15.2 m (49 ft 10...
Macadamia Klasifikasi ilmiah Kerajaan: Plantae (tanpa takson): Angiospermae (tanpa takson): Eudikotil Ordo: Proteales Famili: Proteaceae Genus: MacadamiaF.Muell. Spesies Macadamia claudiensis Macadamia grandis Macadamia hildebrandii Macadamia integrifolia Macadamia jansenii Macadamia ternifolia Macadamia bavana Macadamia tetraphylla Macadamia whelanii Macadamia adalah genus dari delapan spesies tumbuhan dari familia Proteaceae, tersebar di Australia timur (7 spesies), dan Sulawesi. Di Jawa T...
Mountains in Venezuela This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Serranía del Perijá – news · newspapers · books · scholar · JSTOR (September 2023) (Learn how and when to remove this template message) Serranía del PerijáCerro PintaoHighest pointPeakCerro de las TetasElevation3,630 m (11,9...
1995 studio album by Sonny FortuneA Better UnderstandingStudio album by Sonny FortuneReleasedSeptember 12, 1995RecordedFebruary 20 & 21, 1995StudioVan Gelder Studio, Englewood Cliffs, NJGenreJazzLength57:16LabelBlue NoteProducerMarty Khan, Sonny FortuneSonny Fortune chronology Four in One(1994) A Better Understanding(1995) From Now On(1996) A Better Understanding is an album by saxophonist Sonny Fortune which was recorded in 1995 and released on the Blue Note label.[1][...
Mr.Soedarisman Poerwokoesoemo Wali Kota Yogyakarta Ke-2Masa jabatan22 Juli 1947 – 22 September 1966PresidenSoekarnoWakil PresidenBung HattaPendahuluM. EnochPenggantiSoedjono A. Y. Informasi pribadiLahir(1913-10-22)22 Oktober 1913Yogyakarta, Hindia BelandaMeninggal29 Februari 1988(1988-02-29) (umur 74)Yogyakarta, IndonesiaKebangsaanIndonesiaPartai politikPNIAlma materRechtshoogeschool te BataviaSunting kotak info • L • B Kangjeng Pangeran Haryo Soedarisman Poe...
County in Michigan, United States County in MichiganJackson CountyCountyMichigan State Prison SealLocation within the U.S. state of MichiganMichigan's location within the U.S.Coordinates: 42°15′N 84°25′W / 42.25°N 84.42°W / 42.25; -84.42Country United StatesState MichiganOrganizedAugust 1[1], 1832Named forAndrew JacksonSeatJacksonLargest cityJacksonArea • Total723 sq mi (1,870 km2) • Land702 sq ...
متطلبات الحصول على تأشيرة للمواطنين المغاربة هي قيود إدارية تفرضها سلطات الدول الأخرى على المواطنين المغاربة لدخول أراضيها. ابتداءاً من أبريل 2021، يستطيع المغاربة الدخول إلى 65 دولة بدون تأشيرة أو بتأشيرة عند الدخول، حيث يحتل جواز السفر المغربي الرتبة 83 في العالم وفقاً للت...
هانيتشي هانيتشي (زاكارباتسكا) تاريخ التأسيس 1402 تقسيم إداري البلد أوكرانيا الإمبراطورية النمساوية الإمبراطورية النمساوية المجرية خصائص جغرافية إحداثيات 48°07′31″N 23°48′04″E / 48.125277777778°N 23.801111111111°E / 48.125277777778; 23.801111111111 المساحة 560 كيلومتر مربع الارتفا�...
Text with all capital letters For the songs, see All Caps (Madvillain song) and All Caps (Weathers song). The name of the railway engine Mallard, set in all capital letters In typography, text or font in all caps (short for all capitals) contains capital letters without any lowercase letters. For example: THIS TEXT IS IN ALL CAPS. All-caps text can be seen in legal documents, advertisements, newspaper headlines, and the titles on book covers. Short strings of words in capital letters appear b...
جبل المنطار (طولكرم) قمة جبل المنطار الموقع طولكرم الارتفاع 300–500 متر (980–1,640 قدم) السلسلة سلسلة جبال الشمال تعديل مصدري - تعديل جبل المنطار، ويُلقب بـحارس طولكرم، وهو جبل يقع في مدينة طولكرم وتحديدًا عند مدخل المدينة من جهة الشرق، يحيط بالجبل كل من مدينة طولكرم وبلدت...
1800 United States gubernatorial elections ← 1799 March 11, 1800 – December 7, 1800 1801 → 11 state governorships Majority party Minority party Party Federalist Democratic-Republican Last election 10 governorships 6 governorships Seats before 9 7[a] Seats won 7 4 Seats after 9 7 Seat change Seats up 7 4 Democratic-Republican gain Democratic-Republican hold &#...
2012 United States Grand Prix Race 19 of 20 in the 2012 Formula One World Championship← Previous raceNext race → Layout of the Circuit of the AmericasRace details[1]Date 18 November 2012 (2012-11-18)Official name 2012 Formula 1 United States Grand Prix[1]Location Circuit of the AmericasTravis County, Austin, TexasCourse Permanent racing facilityCourse length 5.513 km (3.426 miles)Distance 56 laps, 308.405 km (191.634 miles)Weather Scatter...
ÁlmosKende atau gyula HungariaÁlmos digambarkan di dalam Kronik PiktumBerkuasaskt. 850 – skt. 895PendahuluLevedi (?)PenerusÁrpádKelahiranskt. 820Kematianskt. 895 (usia 75)Transilvania (diperdebatkan)WangsaWangsa ÁrpádAyahÜgyek atau ElődIbuEmeseAnakÁrpádAgamaPaganisme Hungaria Álmos (pengucapan bahasa Hungaria: [ˈaːlmoʃ]), juga Almos[1] atau Almus,[2] (skt. 820 - skt. 895) -sesuai dengan catatan kronik Hungaria merupakan kepala pertama dari federasi be...
Sporting event delegationIceland at the2002 Winter OlympicsIOC codeISLNOCNational Olympic and Sports Association of IcelandWebsitewww.isi.is (in Icelandic)in Salt Lake CityCompetitors6 (4 men, 2 women) in 1 sportFlag bearer Dagný Linda KristjánsdóttirMedals Gold 0 Silver 0 Bronze 0 Total 0 Winter Olympics appearances (overview)19481952195619601964196819721976198019841988199219941998200220062010201420182022 Iceland competed at the 2002 Winter Olympics in Salt Lake City, United Sta...
Dislike of that which is perceived to be foreign or strange Xenophobe redirects here. For other uses, see Xenophobe (disambiguation). Not to be confused with Sinophobia. A 1912 xenophobic cartoon blaming foreigners for threatening economic prosperity in the United States. Part of a series onDiscrimination Forms Institutional Structural Statistical Taste-based Attributes Age Caste Class Dialect Disability Genetic Hair texture Height Language Looks Mental disorder Race / Ethnicity Skin...
