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Long‐term, low‐dose exposure to microcystin toxin does not increase the risk of liver tumor development or growth in mice
Author(s) -
Labine Meaghan,
Minuk Gerald Y.
Publication year - 2015
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12394
Subject(s) - microcystin lr , thioacetamide , cyanotoxin , hepatotoxin , toxicity , toxin , liver cancer , biology , microcystin , medicine , hepatocellular carcinoma , cyanobacteria , endocrinology , cancer research , microbiology and biotechnology , genetics , bacteria
Aim Cyanotoxins are biological toxins produced by cyanobacteria (blue green algae) that have been implicated in the pathogenesis of liver tumors. Based on acute toxicity studies, the W orld H ealth O rganization has designated 1.0 μg/L of cyanotoxin‐contaminated drinking water as the safe allowable limit for daily oral consumption. The aim of this study was to determine whether long‐term exposure to this concentration of cyanotoxins is capable of initiating or promoting the growth of liver tumors. Methods In the present study, four groups of adult, male CD ‐1 mice ( n = 20/group) were exposed to either drinking water alone (water group), drinking water containing 1.0 μg/L of microcystin‐ LR ( MC‐LR group), MC‐LR plus the tumor promoter thioacetamide ( MC‐LR / TAA group) or thioacetamide alone ( TAA group). Following 28 weeks of exposure, mice were killed and the livers examined for tumor number and size. Results No tumors were present in the water or MC‐LR alone groups while five mice in the MC‐LR / TAA group and four in the TAA alone group developed liver tumors. The mean size of the tumors in the MC‐LR / TAA and TAA alone groups were similar as were the results of K i‐67 staining, number of atypical mitoses and liver cancer gene expression profiles. In vitro MC‐LR (0.1–1000 μg/L) exposure did not induce malignant transformation of WB ‐ F 344 hepatic stem cells or increase the proliferative activity or invasiveness of PLC / PRF /5 malignant hepatocytes. Conclusion The results of this study suggest that long‐term, low dose cyanotoxin exposure is unlikely to result in liver tumor development or enhance existing tumor growth.