Long-term, low-dose exposure to microcystin toxin does not increase the risk of liver tumor development or growth in mice.

Abstract

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 World Health Organization 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. 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. 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 Ki-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-F344 hepatic stem cells or increase the proliferative activity or invasiveness of PLC/PRF/5 malignant hepatocytes. 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.