The Role of Microcystins as Liver Cancer Promoters in a Two-Staged Model of Liver Cancer Promotion

Session: 41a. - Great Lakes Harmful Algal Blooms Research from Watershed Influence to Ecosystem Effects

Igor Mrdjen, The Ohio State University, College of Public Health, [email protected]
Jiyoung Lee, The Ohio State University, [email protected]
Christopher Weghorst, The Ohio State University College of Public Health, [email protected]
Thomas Knobloch, The Ohio State University College of Public Health, [email protected]

Abstract

The most common and potent congener of microcystin, microcystin-LR, is a cited "suspected carcinogen", and limited epidemiological data have linked microcystin exposure to increased liver cancer rates. Current preclinical studies are inconclusive, and often rely on intraperitoneal injection or gavage to study MC exposures; methods which may increase stress and bias results. Here, we propose a novel exposure method, avoiding stress. We hypothesized that chronic, in vivo, drinking water exposure to purified micorcystin-LR (MC-LR), or a complex bioactive mixture of lysed Microcystis aeruginosa biomass (LMB), would result in increases of liver lesion incidence and multiplicity. Male C3H/HeJ mice were initiated with a single i.p. injection of diethylnitrosamine (DEN) followed by ad libitum drinking water exposure to either: i) standard drinking water (DW); ii) DW with MC-LR (10ug/L); or DW with LBM (100,000 cells/L [10ug/L total MC equivalent]) beginning 3 weeks after initiation, for 31 weeks. Histopahologic evaluation shows that proportions of hepatocellular carcinomas were signficantly higher in the MC-LR (44%; p=0.02) and LMB (56%; p=0.0073) groups compared to DW (13%). Additionally, Mice treated with LMB had a signifiantly higher mortality rate (35%; p=0.0009) compared to other groups. These data support a promoting role of cyanotxins in liver carcinogenesis, with lesion progression significantly shifting toward carcinoma in the exposure

1. Keyword
human health

2. Keyword
harmful algal blooms

3. Keyword
drinking water

4. Additional Keyword
cancer

5. Additional Keyword
exposure

6. Additional Keyword
microcystin