Drinking Water Exposure to Cyanotoxins in a Two-Staged Model of Liver Cancer Promotion

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Microcystins (MCs) are hepatotoxins produced by over 40 cyanobacterial species found in harmful algal blooms (HABs) reported in fresh waterbodies worldwide. MC-LR, the most common and potent congener of MC can readily be found in eutrophic freshwater, including western Lake Erie. Exposure to MCs and other cyanobacterial hepatotoxins have previously been linked to promotion of liver carcinogenesis and increased liver cancer incidence in pre-clinical and epidemiologic studies. In this pilot study, we hypothesized that chronic ingestion of purified MC-LR (via drinking water) or a complex bioactive mixture, extracted from Microcystis aeruginosa (Lysate), would promote liver cancer development in mice. Three groups of C3H/HeJ mice received one intraperitoneal (i.p.) injection of diethylnitrosamine (DEN, cancer initiator) at 3 weeks of age. Three weeks later we administered ad libitum drinking water exposure to either 1) pure water, 2) water with MC-LR (10 µg/L), 3) water with Lysate (10 µg/L total MC). Exposure concentrations were based on potentially environmentally relevant levels, such as previously established US EPA recreational water MC guidelines. Over the course of the study, mouse weights, amount of food and water consumption were not impacted by toxin ingestion. Upon analysis, we found no significant differences in the number of gross and histopathologic liver lesion counts across treatment groups. However, the proportion of lesions classified as hepatocellular carcinomas in the MC-LR group (44%; p= 0.02) and Lysate (56%; p=0.0073) were significantly higher compared to the pure water group (13%). Mice ingested with Lysate also had a significantly increased mortality (35.6%; p=0.0009), compared to the other groups, over the course of the study. This study uses a exposure model analogous to real-world exposure and avoids stress associated with traditional intraperitoneal and gavage methods. Here, we note the cancer promoting effects of combinatorial exposures to multiple MCs and bioactive compounds of cyanobacterial cells, and mortality associated with chronic relatively low-dose exposure to MCs.


Poster Division: Biological Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)


hepatocellular carcinoma, mortality, Microcystis aeruginosa, cancer promotion, harmful algal blooms, microcystin