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. 2000 Mar;108(Suppl 1):113–122. doi: 10.1289/ehp.00108s1113

Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.

B C Hitzfeld 1, S J Höger 1, D R Dietrich 1
PMCID: PMC1637783  PMID: 10698727

Abstract

Cyanobacteria (blue-green algae) produce toxins that may present a hazard for drinking water safety. These toxins (microcystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), cylindrospermopsin) are structurally diverse and their effects range from liver damage, including liver cancer, to neurotoxicity. The occurrence of cyanobacteria and their toxins in water bodies used for the production of drinking water poses a technical challenge for water utility managers. With respect to their removal in water treatment procedures, of the more than 60 microcystin congeners, microcystin-LR (L, L-leucine; R, L-arginine) is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking. In response to the growing concern about nonlethal acute and chronic effects of microcystins, the World Health Organization has recently set a new provisional guideline value for microcystin-LR of 1.0 microg/L drinking water. This will lead to further efforts by water suppliers to develop effective treatment procedures to remove these toxins. Of the water treatment procedures discussed in this review, chlorination, possibly micro-/ultrafiltration, but especially ozonation are the most effective in destroying cyanobacteria and in removing microcystins. However, these treatments may not be sufficient during bloom situations or when a high organic load is present, and toxin levels should therefore be monitored during the water treatment process. In order to perform an adequate human risk assessment of microcystin exposure via drinking water, the issue of water treatment byproducts will have to be addressed in the future.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen R. J., Luu H. A., Chen D. Z., Holmes C. F., Kent M. L., Le Blanc M., Taylor F. J., Williams D. E. Chemical and biological evidence links microcystins to salmon 'netpen liver disease'. Toxicon. 1993 Oct;31(10):1315–1323. doi: 10.1016/0041-0101(93)90404-7. [DOI] [PubMed] [Google Scholar]
  2. Botes D. P., Kruger H., Viljoen C. C. Isolation and characterization of four toxins from the blue-green alga, Microcystis aeruginosa. Toxicon. 1982;20(6):945–954. doi: 10.1016/0041-0101(82)90097-6. [DOI] [PubMed] [Google Scholar]
  3. Botes D. P., Viljoen C. C., Kruger H., Wessels P. L., Williams D. H. Configuration assignments of the amino acid residues and the presence of N-methyldehydroalanine in toxins from the blue-green alga, Microcystis aeruginosa. Toxicon. 1982;20(6):1037–1042. doi: 10.1016/0041-0101(82)90105-2. [DOI] [PubMed] [Google Scholar]
  4. Brooks W. P., Codd G. A. Distribution of Microcystis aeruginosa peptide toxin and interactions with hepatic microsomes in mice. Pharmacol Toxicol. 1987 Mar;60(3):187–191. doi: 10.1111/j.1600-0773.1987.tb01731.x. [DOI] [PubMed] [Google Scholar]
  5. Carmichael W. W., Beasley V., Bunner D. L., Eloff J. N., Falconer I., Gorham P., Harada K., Krishnamurthy T., Yu M. J., Moore R. E. Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae). Toxicon. 1988;26(11):971–973. doi: 10.1016/0041-0101(88)90195-x. [DOI] [PubMed] [Google Scholar]
  6. Carmichael W. W., Biggs D. F., Gorham P. R. Toxicology and pharmacological action of anabaena flos-aquae toxin. Science. 1975 Feb 14;187(4176):542–544. doi: 10.1126/science.803708. [DOI] [PubMed] [Google Scholar]
  7. Carmichael W. W. Cyanobacteria secondary metabolites--the cyanotoxins. J Appl Bacteriol. 1992 Jun;72(6):445–459. doi: 10.1111/j.1365-2672.1992.tb01858.x. [DOI] [PubMed] [Google Scholar]
  8. Carmichael W. W., Eschedor J. T., Patterson G. M., Moore R. E. Toxicity and partial structure of a hepatotoxic peptide produced by the cyanobacterium Nodularia spumigena Mertens emend. L575 from New Zealand. Appl Environ Microbiol. 1988 Sep;54(9):2257–2263. doi: 10.1128/aem.54.9.2257-2263.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Craig M., Luu H. A., McCready T. L., Williams D., Andersen R. J., Holmes C. F. Molecular mechanisms underlying he interaction of motuporin and microcystins with type-1 and type-2A protein phosphatases. Biochem Cell Biol. 1996;74(4):569–578. doi: 10.1139/o96-061. [DOI] [PubMed] [Google Scholar]
  10. Dittmann E., Neilan B. A., Erhard M., von Döhren H., Börner T. Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806. Mol Microbiol. 1997 Nov;26(4):779–787. doi: 10.1046/j.1365-2958.1997.6131982.x. [DOI] [PubMed] [Google Scholar]
  11. Edwards C., Beattie K. A., Scrimgeour C. M., Codd G. A. Identification of anatoxin-A in benthic cyanobacteria (blue-green algae) and in associated dog poisonings at Loch Insh, Scotland. Toxicon. 1992 Oct;30(10):1165–1175. doi: 10.1016/0041-0101(92)90432-5. [DOI] [PubMed] [Google Scholar]
  12. Eriksson J. E., Grönberg L., Nygård S., Slotte J. P., Meriluoto J. A. Hepatocellular uptake of 3H-dihydromicrocystin-LR, a cyclic peptide toxin. Biochim Biophys Acta. 1990 Jun 11;1025(1):60–66. doi: 10.1016/0005-2736(90)90190-y. [DOI] [PubMed] [Google Scholar]
  13. Eriksson J. E., Paatero G. I., Meriluoto J. A., Codd G. A., Kass G. E., Nicotera P., Orrenius S. Rapid microfilament reorganization induced in isolated rat hepatocytes by microcystin-LR, a cyclic peptide toxin. Exp Cell Res. 1989 Nov;185(1):86–100. doi: 10.1016/0014-4827(89)90039-6. [DOI] [PubMed] [Google Scholar]
  14. Eriksson J. E., Toivola D., Meriluoto J. A., Karaki H., Han Y. G., Hartshorne D. Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1347–1353. doi: 10.1016/s0006-291x(05)80936-2. [DOI] [PubMed] [Google Scholar]
  15. Falconer I. R., Beresford A. M., Runnegar M. T. Evidence of liver damage by toxin from a bloom of the blue-green alga, Microcystis aeruginosa. Med J Aust. 1983 May 28;1(11):511–514. doi: 10.5694/j.1326-5377.1983.tb136192.x. [DOI] [PubMed] [Google Scholar]
  16. Falconer I. R., Buckley T., Runnegar M. T. Biological half-life, organ distribution and excretion of 125-I-labelled toxic peptide from the blue-green alga Microcystis aeruginosa. Aust J Biol Sci. 1986;39(1):17–21. [PubMed] [Google Scholar]
  17. Falconer I. R., Smith J. V., Jackson A. R., Jones A., Runnegar M. T. Oral toxicity of a bloom of the Cyanobacterium microcystis Aeruginosa administered to mice over periods up to 1 year. J Toxicol Environ Health. 1988;24(3):291–305. doi: 10.1080/15287398809531163. [DOI] [PubMed] [Google Scholar]
  18. Fujiki H. Is the inhibition of protein phosphatase 1 and 2A activities a general mechanism of tumor promotion in human cancer development? Mol Carcinog. 1992;5(2):91–94. doi: 10.1002/mc.2940050202. [DOI] [PubMed] [Google Scholar]
  19. Fujiki H., Suganuma M. Unique features of the okadaic acid activity class of tumor promoters. J Cancer Res Clin Oncol. 1999;125(3-4):150–155. doi: 10.1007/s004320050257. [DOI] [PubMed] [Google Scholar]
  20. Fujiki H., Suganuma M., Yoshizawa S., Kanazawa H., Sugimura T., Manam S., Kahn S. M., Jiang W., Hoshina S., Weinstein I. B. Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters. Mol Carcinog. 1989;2(4):184–187. doi: 10.1002/mc.2940020403. [DOI] [PubMed] [Google Scholar]
  21. Harada K., Matsuura K., Suzuki M., Watanabe M. F., Oishi S., Dahlem A. M., Beasley V. R., Carmichael W. W. Isolation and characterization of the minor components associated with microcystins LR and RR in the cyanobacterium (blue-green algae). Toxicon. 1990;28(1):55–64. doi: 10.1016/0041-0101(90)90006-s. [DOI] [PubMed] [Google Scholar]
  22. Harada K., Murata H., Qiang Z., Suzuki M., Kondo F. Mass spectrometric screening method for microcystins in cyanobacteria. Toxicon. 1996 Jun;34(6):701–710. doi: 10.1016/0041-0101(95)00163-8. [DOI] [PubMed] [Google Scholar]
  23. Harada K., Oshikata M., Uchida H., Suzuki M., Kondo F., Sato K., Ueno Y., Yu S. Z., Chen G., Chen G. C. Detection and identification of microcystins in the drinking water of Haimen City, China. Nat Toxins. 1996;4(6):277–283. doi: 10.1002/(SICI)(1996)4:6<277::AID-NT5>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  24. Hawkins P. R., Runnegar M. T., Jackson A. R., Falconer I. R. Severe hepatotoxicity caused by the tropical cyanobacterium (blue-green alga) Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju isolated from a domestic water supply reservoir. Appl Environ Microbiol. 1985 Nov;50(5):1292–1295. doi: 10.1128/aem.50.5.1292-1295.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hooser S. B., Beasley V. R., Lovell R. A., Carmichael W. W., Haschek W. M. Toxicity of microcystin LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa, to rats and mice. Vet Pathol. 1989 May;26(3):246–252. doi: 10.1177/030098588902600309. [DOI] [PubMed] [Google Scholar]
  26. Ito E., Kondo F., Harada K. Hepatic necrosis in aged mice by oral administration of microcystin-LR. Toxicon. 1997 Feb;35(2):231–239. doi: 10.1016/s0041-0101(96)00129-8. [DOI] [PubMed] [Google Scholar]
  27. Ito E., Kondo F., Terao K., Harada K. Neoplastic nodular formation in mouse liver induced by repeated intraperitoneal injections of microcystin-LR. Toxicon. 1997 Sep;35(9):1453–1457. doi: 10.1016/s0041-0101(97)00026-3. [DOI] [PubMed] [Google Scholar]
  28. James K. J., Sherlock I. R., Stack M. A. Anatoxin-a in Irish freshwater and cyanobacteria, determined using a new fluorimetric liquid chromatographic method. Toxicon. 1997 Jun;35(6):963–971. doi: 10.1016/s0041-0101(96)00201-2. [DOI] [PubMed] [Google Scholar]
  29. Jochimsen E. M., Carmichael W. W., An J. S., Cardo D. M., Cookson S. T., Holmes C. E., Antunes M. B., de Melo Filho D. A., Lyra T. M., Barreto V. S. Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med. 1998 Mar 26;338(13):873–878. doi: 10.1056/NEJM199803263381304. [DOI] [PubMed] [Google Scholar]
  30. Krishnamurthy T., Szafraniec L., Hunt D. F., Shabanowitz J., Yates J. R., 3rd, Hauer C. R., Carmichael W. W., Skulberg O., Codd G. A., Missler S. Structural characterization of toxic cyclic peptides from blue-green algae by tandem mass spectrometry. Proc Natl Acad Sci U S A. 1989 Feb;86(3):770–774. doi: 10.1073/pnas.86.3.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Luukkainen R., Sivonen K., Namikoshi M., Färdig M., Rinehart K. L., Niemelä S. I. Isolation and identification of eight microcystins from thirteen Oscillatoria agardhii strains and structure of a new microcystin. Appl Environ Microbiol. 1993 Jul;59(7):2204–2209. doi: 10.1128/aem.59.7.2204-2209.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. MacKintosh R. W., Dalby K. N., Campbell D. G., Cohen P. T., Cohen P., MacKintosh C. The cyanobacterial toxin microcystin binds covalently to cysteine-273 on protein phosphatase 1. FEBS Lett. 1995 Sep 11;371(3):236–240. doi: 10.1016/0014-5793(95)00888-g. [DOI] [PubMed] [Google Scholar]
  33. Mahmood N. A., Carmichael W. W. Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17. Toxicon. 1987;25(11):1221–1227. doi: 10.1016/0041-0101(87)90140-1. [DOI] [PubMed] [Google Scholar]
  34. Mahmood N. A., Carmichael W. W. Paralytic shellfish poisons produced by the freshwater cyanobacterium Aphanizomenon flos-aquae NH-5. Toxicon. 1986;24(2):175–186. doi: 10.1016/0041-0101(86)90120-0. [DOI] [PubMed] [Google Scholar]
  35. Mahmood N. A., Carmichael W. W., Pfahler D. Anticholinesterase poisonings in dogs from a cyanobacterial (blue-green algae) bloom dominated by Anabaena flos-aquae. Am J Vet Res. 1988 Apr;49(4):500–503. [PubMed] [Google Scholar]
  36. Matsushima R., Yoshizawa S., Watanabe M. F., Harada K., Furusawa M., Carmichael W. W., Fujiki H. In vitro and in vivo effects of protein phosphatase inhibitors, microcystins and nodularin, on mouse skin and fibroblasts. Biochem Biophys Res Commun. 1990 Sep 14;171(2):867–874. doi: 10.1016/0006-291x(90)91226-i. [DOI] [PubMed] [Google Scholar]
  37. Meissner K., Dittmann E., Börner T. Toxic and non-toxic strains of the cyanobacterium Microcystis aeruginosa contain sequences homologous to peptide synthetase genes. FEMS Microbiol Lett. 1996 Jan 15;135(2-3):295–303. doi: 10.1111/j.1574-6968.1996.tb08004.x. [DOI] [PubMed] [Google Scholar]
  38. Meriluoto J. A., Sandström A., Eriksson J. E., Remaud G., Craig A. G., Chattopadhyaya J. Structure and toxicity of a peptide hepatotoxin from the cyanobacterium Oscillatoria agardhii. Toxicon. 1989;27(9):1021–1034. doi: 10.1016/0041-0101(89)90153-0. [DOI] [PubMed] [Google Scholar]
  39. Miller A. P., Tisdale E. S. PUBLIC HEALTH ENGINEERING: EPIDEMIC OF INTESTINAL DISORDERS IN CHARLESTION, W. VA., OCCURRING SIMULTANEOUSLY WITH UNPRECEDENTED WATER SUPPLY CONDITIONS. Am J Public Health Nations Health. 1931 Feb;21(2):198–200. doi: 10.2105/ajph.21.2.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Namikoshi M., Sivonen K., Evans W. R., Carmichael W. W., Sun F., Rouhiainen L., Luukkainen R., Rinehart K. L. Two new L-serine variants of microcystins-LR and -RR from Anabaena sp. strains 202 A1 and 202 A2. Toxicon. 1992 Nov;30(11):1457–1464. doi: 10.1016/0041-0101(92)90521-6. [DOI] [PubMed] [Google Scholar]
  41. Negri A. P., Jones G. J. Bioaccumulation of paralytic shellfish poisoning (PSP) toxins from the cyanobacterium Anabaena circinalis by the freshwater mussel Alathyria condola. Toxicon. 1995 May;33(5):667–678. doi: 10.1016/0041-0101(94)00180-g. [DOI] [PubMed] [Google Scholar]
  42. Neilan B. A., Jacobs D., Del Dot T., Blackall L. L., Hawkins P. R., Cox P. T., Goodman A. E. rRNA sequences and evolutionary relationships among toxic and nontoxic cyanobacteria of the genus Microcystis. Int J Syst Bacteriol. 1997 Jul;47(3):693–697. doi: 10.1099/00207713-47-3-693. [DOI] [PubMed] [Google Scholar]
  43. Neilan B. A., Jacobs D., Goodman A. E. Genetic diversity and phylogeny of toxic cyanobacteria determined by DNA polymorphisms within the phycocyanin locus. Appl Environ Microbiol. 1995 Nov;61(11):3875–3883. doi: 10.1128/aem.61.11.3875-3883.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Nishiwaki-Matsushima R., Ohta T., Nishiwaki S., Suganuma M., Kohyama K., Ishikawa T., Carmichael W. W., Fujiki H. Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol. 1992;118(6):420–424. doi: 10.1007/BF01629424. [DOI] [PubMed] [Google Scholar]
  45. Ohta T., Sueoka E., Iida N., Komori A., Suganuma M., Nishiwaki R., Tatematsu M., Kim S. J., Carmichael W. W., Fujiki H. Nodularin, a potent inhibitor of protein phosphatases 1 and 2A, is a new environmental carcinogen in male F344 rat liver. Cancer Res. 1994 Dec 15;54(24):6402–6406. [PubMed] [Google Scholar]
  46. Park H. D., Watanabe M. F., Harda K., Nagai H., Suzuki M., Watanabe M., Hayashi H. Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters. Nat Toxins. 1993;1(6):353–360. doi: 10.1002/nt.2620010606. [DOI] [PubMed] [Google Scholar]
  47. Pilotto L. S., Douglas R. M., Burch M. D., Cameron S., Beers M., Rouch G. J., Robinson P., Kirk M., Cowie C. T., Hardiman S. Health effects of exposure to cyanobacteria (blue-green algae) during recreational water-related activities. Aust N Z J Public Health. 1997 Oct;21(6):562–566. doi: 10.1111/j.1467-842x.1997.tb01755.x. [DOI] [PubMed] [Google Scholar]
  48. Pouria S., de Andrade A., Barbosa J., Cavalcanti R. L., Barreto V. T., Ward C. J., Preiser W., Poon G. K., Neild G. H., Codd G. A. Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil. Lancet. 1998 Jul 4;352(9121):21–26. doi: 10.1016/s0140-6736(97)12285-1. [DOI] [PubMed] [Google Scholar]
  49. Rao P. V., Bhattacharya R. The cyanobacterial toxin microcystin-LR induced DNA damage in mouse liver in vivo. Toxicology. 1996 Nov 15;114(1):29–36. doi: 10.1016/s0300-483x(96)03413-0. [DOI] [PubMed] [Google Scholar]
  50. Rapala J., Sivonen K., Lyra C., Niemelä S. I. Variation of microcystins, cyanobacterial hepatotoxins, in Anabaena spp. as a function of growth stimuli. Appl Environ Microbiol. 1997 Jun;63(6):2206–2212. doi: 10.1128/aem.63.6.2206-2212.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Robinson N. A., Miura G. A., Matson C. F., Dinterman R. E., Pace J. G. Characterization of chemically tritiated microcystin-LR and its distribution in mice. Toxicon. 1989;27(9):1035–1042. doi: 10.1016/0041-0101(89)90154-2. [DOI] [PubMed] [Google Scholar]
  52. Rudi K., Skulberg O. M., Larsen F., Jakobsen K. S. Quantification of toxic cyanobacteria in water by use of competitive PCR followed by sequence-specific labeling of oligonucleotide probes. Appl Environ Microbiol. 1998 Jul;64(7):2639–2643. doi: 10.1128/aem.64.7.2639-2643.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Rudolph-Böhner S., Mierke D. F., Moroder L. Molecular structure of the cyanobacterial tumor-promoting microcystins. FEBS Lett. 1994 Aug 8;349(3):319–323. doi: 10.1016/0014-5793(94)00680-6. [DOI] [PubMed] [Google Scholar]
  54. Runnegar M. T., Andrews J., Gerdes R. G., Falconer I. R. Injury to hepatocytes induced by a peptide toxin from the cyanobacterium Microcystis aeruginosa. Toxicon. 1987;25(11):1235–1239. doi: 10.1016/0041-0101(87)90142-5. [DOI] [PubMed] [Google Scholar]
  55. Runnegar M. T., Falconer I. R., Buckley T., Jackson A. R. Lethal potency and tissue distribution of 125I-labelled toxic peptides from the blue-green alga Microcystis aeruginosa. Toxicon. 1986;24(5):506–509. doi: 10.1016/0041-0101(86)90083-8. [DOI] [PubMed] [Google Scholar]
  56. Runnegar M. T., Falconer I. R. Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. Toxicon. 1986;24(2):109–115. doi: 10.1016/0041-0101(86)90112-1. [DOI] [PubMed] [Google Scholar]
  57. Runnegar M. T., Falconer I. R., Silver J. Deformation of isolated rat hepatocytes by a peptide hepatotoxin from the blue-green alga microcystis aeruginosa. Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):268–272. doi: 10.1007/BF00503829. [DOI] [PubMed] [Google Scholar]
  58. Runnegar M. T., Maddatu T., Deleve L. D., Berndt N., Govindarajan S. Differential toxicity of the protein phosphatase inhibitors microcystin and calyculin A. J Pharmacol Exp Ther. 1995 Apr;273(1):545–553. [PubMed] [Google Scholar]
  59. Runnegar M., Berndt N., Kong S. M., Lee E. Y., Zhang L. In vivo and in vitro binding of microcystin to protein phosphatases 1 and 2A. Biochem Biophys Res Commun. 1995 Nov 2;216(1):162–169. doi: 10.1006/bbrc.1995.2605. [DOI] [PubMed] [Google Scholar]
  60. Shephard G. S., Stockenström S., De Villiers D., Engelbrecht W. J., Sydenham E. W., Wessels G. F. Photocatalytic degradation of cyanobacterial microcystin toxins in water. Toxicon. 1998 Dec;36(12):1895–1901. doi: 10.1016/s0041-0101(98)00110-x. [DOI] [PubMed] [Google Scholar]
  61. Sivonen K. Effects of light, temperature, nitrate, orthophosphate, and bacteria on growth of and hepatotoxin production by Oscillatoria agardhii strains. Appl Environ Microbiol. 1990 Sep;56(9):2658–2666. doi: 10.1128/aem.56.9.2658-2666.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sivonen K., Kononen K., Carmichael W. W., Dahlem A. M., Rinehart K. L., Kiviranta J., Niemela S. I. Occurrence of the hepatotoxic cyanobacterium Nodularia spumigena in the Baltic Sea and structure of the toxin. Appl Environ Microbiol. 1989 Aug;55(8):1990–1995. doi: 10.1128/aem.55.8.1990-1995.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sivonen K., Namikoshi M., Evans W. R., Carmichael W. W., Sun F., Rouhiainen L., Luukkainen R., Rinehart K. L. Isolation and characterization of a variety of microcystins from seven strains of the cyanobacterial genus Anabaena. Appl Environ Microbiol. 1992 Aug;58(8):2495–2500. doi: 10.1128/aem.58.8.2495-2500.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stotts R. R., Twardock A. R., Haschek W. M., Choi B. W., Rinehart K. L., Beasley V. R. Distribution of tritiated dihydromicrocystin in swine. Toxicon. 1997 Jun;35(6):937–953. doi: 10.1016/s0041-0101(96)00169-9. [DOI] [PubMed] [Google Scholar]
  65. Stotts R. R., Twardock A. R., Koritz G. D., Haschek W. M., Manuel R. K., Hollis W. B., Beasley V. R. Toxicokinetics of tritiated dihydromicrocystin-LR in swine. Toxicon. 1997 Mar;35(3):455–465. doi: 10.1016/s0041-0101(96)00120-1. [DOI] [PubMed] [Google Scholar]
  66. Sueoka E., Sueoka N., Okabe S., Kozu T., Komori A., Ohta T., Suganuma M., Kim S. J., Lim I. K., Fujiki H. Expression of the tumor necrosis factor alpha gene and early response genes by nodularin, a liver tumor promoter, in primary cultured rat hepatocytes. J Cancer Res Clin Oncol. 1997;123(8):413–419. doi: 10.1007/BF01372544. [DOI] [PubMed] [Google Scholar]
  67. Suzuki H., Watanabe M. F., Wu Y., Sugita T., Kita K., Sato T., Wang X., Tanzawa H., Sekiya S., Suzuki N. Mutagenicity of microcystin-LR in human RSa cells. Int J Mol Med. 1998 Jul;2(1):109–112. doi: 10.3892/ijmm.2.1.109. [DOI] [PubMed] [Google Scholar]
  68. Teixeira M. da G., Costa M. da C., de Carvalho V. L., Pereira M. dos S., Hage E. Gastroenteritis epidemic in the area of the Itaparica Dam, Bahia, Brazil. Bull Pan Am Health Organ. 1993;27(3):244–253. [PubMed] [Google Scholar]
  69. Toivola D. M., Eriksson J. E., Brautigan D. L. Identification of protein phosphatase 2A as the primary target for microcystin-LR in rat liver homogenates. FEBS Lett. 1994 May 16;344(2-3):175–180. doi: 10.1016/0014-5793(94)00382-3. [DOI] [PubMed] [Google Scholar]
  70. Tsuji K., Watanuki T., Kondo F., Watanabe M. F., Suzuki S., Nakazawa H., Suzuki M., Uchida H., Harada K. I. Stability of microcystins from cyanobacteria--II. Effect of UV light on decomposition and isomerization. Toxicon. 1995 Dec;33(12):1619–1631. doi: 10.1016/0041-0101(95)00101-8. [DOI] [PubMed] [Google Scholar]
  71. Turner P. C., Gammie A. J., Hollinrake K., Codd G. A. Pneumonia associated with contact with cyanobacteria. BMJ. 1990 Jun 2;300(6737):1440–1441. doi: 10.1136/bmj.300.6737.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Ueno Y., Nagata S., Tsutsumi T., Hasegawa A., Watanabe M. F., Park H. D., Chen G. C., Chen G., Yu S. Z. Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay. Carcinogenesis. 1996 Jun;17(6):1317–1321. doi: 10.1093/carcin/17.6.1317. [DOI] [PubMed] [Google Scholar]
  73. Wickstrom M., Haschek W., Henningsen G., Miller L. A., Wyman J., Beasley V. Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers. Nat Toxins. 1996;4(5):195–205. doi: 10.1002/(SICI)(1996)4:5<195::AID-NT1>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
  74. Yoshida T., Makita Y., Nagata S., Tsutsumi T., Yoshida F., Sekijima M., Tamura S., Ueno Y. Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice. Nat Toxins. 1997;5(3):91–95. doi: 10.1002/1522-7189(1997)5:3<91::AID-NT1>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]
  75. Yoshizawa S., Matsushima R., Watanabe M. F., Harada K., Ichihara A., Carmichael W. W., Fujiki H. Inhibition of protein phosphatases by microcystins and nodularin associated with hepatotoxicity. J Cancer Res Clin Oncol. 1990;116(6):609–614. doi: 10.1007/BF01637082. [DOI] [PubMed] [Google Scholar]
  76. Zilberg B. Gastroenteritis in Salisbury. European children--a five-year study. Cent Afr J Med. 1966 Sep;12(9):164–168. [PubMed] [Google Scholar]

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