Abstract
Cyanobacteria or blue-green algae are becoming increasingly abundant in North American fresh water lakes. Toxins produced by cyanobacteria have been associated with gastrointestinal injury, liver failure, and nephrotoxicity. They have also been implicated in the pathogenesis of gastrointestinal and liver cancers. The purpose of the present study was to determine whether the incidence rates of gastrointestinal, liver, and urologic cancers are increasing in the province of Manitoba and, if so, whether these increases spatially and/or temporally correlate with areas where cyanobacterial contamination of fresh water lakes have been identified. Cancer incidence data were obtained from the Manitoba Cancer Registry. Cyanobacterial contamination data, as reflected by microcystin toxin concentrations, were available from the Manitoba Water Stewardship. ArcGIS mapping was employed to document spatial and temporal relationships between cancer incidence and cyanobacterial data. The results revealed that although the incidence rates for all three cancers have increased over the past 20–25 years, these increases were not disproportionally higher in zones with high microcystin toxin determinations. The results of this study argue against increased exposure to cyanotoxins as an explanation for the increase in gastrointestinal, liver and urologic cancers in Manitoba.
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Beasley VR, Lovell RA, Holmes KR, Walcott HE, Schaeffer DJ, Hoffmann WE, Carmichael WW (2000 Oct 27) Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularly dosed swine. J Toxicol Environ Health A 61(4):281–303
Bouaicha N, Maatouk I (2004 Mar 14) Microcystin-LR and nodularin induce intracellular glutathione alteration, reactive oxygen species production and lipid peroxidation in primary cultured rat hepatocytes. Toxicol Lett 148(1–2):53–63
Fischer A, Hoeger SJ, Stemmer K, Feurstein DJ, Knobeloch D, Nussler A, Dietrich DR (2010 May 15) The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol Appl Pharmacol 245(1):9–20
Fleming LE, Rivero C, Burns J, Williams C, Bean JA, Shea KA, Stinn J (2002 Jun) Blue green algal (cyanobacterial) toxins, surface drinking water, and liver cancer in Florida. Harmful Algae 1(2):157–168
Gaudin J, Le Hegarat L, Nesslany F, Marzin D, Fessard V (2009 Apr) In vivo genotoxic potential of microcystin-LR: a cyanobacterial toxin, investigated both by the unscheduled DNA synthesis (UDS) and the comet assays after intravenous administration. Environ Toxicol 24(2):200–209
Guzman RE, Solter PF, Runnegar MT (2003 Jun) Inhibition of nuclear protein phosphatase activity in mouse hepatocytes by the cyanobacterial toxin microcystin-LR. Toxicon. 41(7):773–781
Ito E, Kondo F, Harada K (2001) Intratracheal administration of microcystin-LR, and its distribution. Toxicon. 39(2–3):265–271
Kulldorf M. 2009. Satscan 8.0, software for spatial and space-time scan statistics. Boston, MA, Information Management Services Inc.
La-Salete R, Oliveira MM, Palmeira CA, Almeida J, Peixoto FP (2008 Jan) Mitochondria a key role in microcystin-LR kidney intoxication. J Appl Toxicol 28(1):55–62
Levesque B, Gervais MC, Chevalier P, Gauvin D, Anassout-Laouan-Sidi E, Gingras S et al (2014) Prospective study of acute health effects in relation to exposure to cyanobacteria. Sci Total Environ 466–467:397–403
Lin H, Liu W, Zeng H, Pu C, Zhang R, Qiu Z, Chen JA, Wang L, Tan Y, Zheng C, Yang X, Tian Y, Huang Y, Luo J, Luo Y, Feng X, Xiao G, Feng L, Li H, Wang F, Yuan C, Wang J, Zhou Z, Wei T, Zuo Y, Wu L, He L, Guo Y, Shu W (2016 May) Determination of environmental exposure to microcystin and aflatoxin as a risk for renal function based on 5493 rural people in Southwest China. Environ Sci Technol 50(10):5346–5356
Milutinovic A, Sedmak B, Horvat-Znidarsic I, Suput D (2002) Renal injuries induced by chronic intoxication with microcystins. Cell Mol Biol Lett 7(1):139–141
Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K, Ishikawa T, Carmichael WW, Fujiki H (1992) Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol 118(6):420–424
Nobre AC, Jorge MC, Menezes DB, Fonteles MC, Monteiro HS (1999 Aug) Effects of microcystin-LR in isolated perfused rat kidney. Bra J Med Biol Res 32(8):985–988
Ohta T, Nishiwaki R, Yatsunami J, Komori A, Suganuma M, Fujiki H (1992 Dec) Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes. Carcinogenesis. 13(12):2443–2447
Orihel DM, Bird DF, Brylinsky M, Chen H, Donald DB, Huang DY, Giani A, Kinniburgh D, Kling H, Kotak BG, Leavitt PR, Nielsen CC, Reedyk S, Rooney RC, Watson SB, Zurawell RW, Vinebrooke RD (2012) High microcystin concentrations occur only at low nitrogen-to-phosphorus ratios in nutrient-rich Canadian lakes. Can J Fish Aquat Sci 69:1457–1462
Robinson NA, Pace JG, Matson CF, Miura GA, Lawrence WB (1991 Jan) Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice. J Pharmacol Exp Ther 256(1):176–182
Soward TE. Evaluation of cancer from exposure to cyanotoxins in drinking water at Grand Lake Saint Marys. Master thesis, Wright State University 2011
Svircev Z, Krstic S, Miladinov-Mikov M, Baltic V, Vidovic M (2009 Jan) Freshwater cyanobacterial blooms and primary liver cancer epidemiological studies in Serbia. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27(1):36–55
Svircev Z, Drobac D, Tokodi N, Vidovic M, Simeunovic J, Miladinov-Mikov M et al (2013) Epidemiology of primary liver cancer in Serbia and possible connection with cyanobacterial blooms. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 31(3):181–200
Svircev Z, Drobac D, Tokodi N, Luzanin Z, Munjas AM, Nikolin B et al (2014) Epidemiology of cancers in Serbia and possible connection with cyanobacterial blooms. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev. 32(4):319–337
Svircev Z, Drobac D, Tokodi N, Mijovic B, Codd GA, Meriluoto J (2017 Feb) Toxicology of microcystins with reference to cases of human intoxications and epidemiological investigations of exposures to cyanobacteria and cyanotoxins. Arch Toxicol 91(2):621–650
Wang Q, Xie P, Chen J, Liang G (2008 Nov) Distribution of microcystins in various organs (heart, liver, intestine, gonad, brain, kidney and lung) of Wistar rat via intravenous injection. Toxicon. 52(6):721–727
Yu SZ, Chen W, Li J (1995 Feb) The prospective research of risk factors of primary liver cancer in Nanhui County, Shanghai. Zhonghua Liu Xing Bing Xue Za Zhi 16(1):22–24
Yu S, Zhao N, Zi X (2001 Mar) The relationship between cyanotoxin (microcystin, MC) in pond-ditch water and primary liver cancer in China. Zhonghua Zhong Liu Za Zhi 23(2):96–99
Zhang F, Lee J, Liang S, Shum CK (2015 May 7) Cyanobacteria blooms and non-alcoholic liver disease: evidence from a county level ecological study in the United States. Environ Health 14:41. https://doi.org/10.1186/s12940-015-0026-7
Zhou L, Yu H, Chen K (2002 Jun) Relationship between microcystin in drinking water and colorectal cancer. Biomed Environ Sci 15(2):166–171
Zhu Y, Zhong X, Zheng S, Ge Z, Du Q, Zhang S (2005 Jul) Transformation of immortalized colorectal crypt cells by microcystin involving constitutive activation of Akt and MAPK cascade. Carcinogenesis. 26(7):1207–1214
Acknowledgments
The authors would like to thank Ms. R. Vizniak for her prompt and accurate typing of the manuscript.
Funding
This research was supported by a grant from the Public Health Agency of Canada and Manitoba Water Stewardship Fund. Ms. M. Labine is a recipient of a Manitoba Health Research Council fellowship award.
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The study was approved by the University of Manitoba Conjoint Ethics Committee.
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Labine, M.A., Shu, E., Xue, L. et al. A lack of association between increases in gastrointestinal, liver, and urologic cancers and cyanobacterial contamination of fresh water lakes in Manitoba. Environ Sci Pollut Res 27, 35852–35858 (2020). https://doi.org/10.1007/s11356-020-09731-y
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DOI: https://doi.org/10.1007/s11356-020-09731-y