Journal
TOXICOLOGY
Volume 487, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2023.153470
Keywords
Cyanotoxins; Microcystin; Nodularin; Cylindrospermopsin; Liver; Cancer
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Cyanobacteria, found worldwide in aquatic and terrestrial environments, can produce hepatotoxins. Human exposure to cyanobacteria and cyanotoxins mainly occurs through contaminated drinking water and food sources. A study on HCC patients in Hawaii showed that cyanotoxins were present in all the patients, with the highest levels in cases related to metabolic risk factors such as hyperlipidemia, type 2 diabetes, and fatty liver disease. Cyanotoxin levels were correlated with tumor expression of genes associated with lipid metabolism. This study suggests that dysregulation of lipid metabolism and progression of hepatic steatosis may play a role in the pathogenesis of HCC.
Cyanobacteria are ubiquitous in aquatic and terrestrial environments worldwide and include a number of species producing tumor-promoting hepatotoxins. Human exposure to cyanobacteria and cyanotoxins primarily occurs though ingestion of contaminated drinking water and food sources. In a Northeast U.S. population, we recently reported an independent association of oral cyanobacteria with risk of hepatocellular carcinoma (HCC). In a cross-sectional study of 55 HCC patients in Hawaii, U.S.A., serum microcystin/nodularin (MC/NOD), cylin-drospermopsin (CYN), and anabaenopeptin (AB) were measured by ELISA. In a subset of 16 patients, cyanotoxin levels were compared by tumor expression of over 700 genes analyzed via the Nanostring nCounter Fibrosis panel. MC/NOD, CYN, and AB were detected in all HCC patients. MC/NOD and CYN levels significantly varied by etiology with the highest levels in cases attributed to metabolic risk factors, specifically, hyperlipidemia, type 2 diabetes, and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. Cyanotoxin levels were significantly positively correlated with tumor expression of genes functioning in PPAR signaling and lipid metabolism. Our study provides novel albeit limited evidence that cyanotoxins may a role in the pathogenesis of HCC through the dysregulation of lipid metabolism and progression of hepatic steatosis.
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