First study to show that microginins are genotoxic

Abstract from a paper by Ujvarosi et al. (2019), published in Chemospere :

Microginins (MGs) are bioactive metabolites mainly produced by Microcystis spp., (Cyanobacteria) commonly found in eutrophic environments. In this study, the cytotoxic and genotoxic activities of four MG congeners (MG FR3, MG GH787, cyanostatin B, MGL 402) and a well characterized cyanobacterial extract B-14-01 containing these metabolites were evaluated in the human hepatocellular carcinoma (HepG2) cell line. The cytotoxicity was measured with the MTT assay, while genotoxicity was studied with the comet, γH2AX and cytokinesis block (CBMN) micronucleus assays. The viability of cells after 24 h was significantly affected only by the extract, whereas after 72 h a concentration dependent decrease in cell proliferation was observed for the extract and tested microginins, with MGL 402 being the most potent and MG FR3 the least potent congener. The extract and all tested congeners induced DNA strand breaks after 4 and 24 h exposure. The most potent was the extract, which induced concentration and time dependent increase in DNA damage at concentrations ≥0.01 μg mL−1. Among microginins the most potent was MGL 402 (increase in DNA strand breaks at ≥ 0.01 μg mL−1) and MG FR3 was the least potent (increase in DNA strand breaks at ≥ 1 μg mL−1). However, no induction of DNA double strand breaks was observed after 24 and 72-h exposure to the cyanobacterial extract or MGs. Induction of genomic instability was observed in cells exposed to MG GH787, cyanostatin B and the extract B-14-01. This study is the first to provide the evidence that microginins exert genotoxic activity.

The paper is a product of joined research by groups in Slovenia and Hungary and features CYANOCOST members Bojana Zegura, Gabor Vasas, Klara Hercog, Metka Filipic. The authors acknowledge CYANOCOST.

Reference:

Andrea Zsuzsanna Ujvárosi, Klara Hercog, Milán Riba, Sándor Gonda, Metka Filipič, Gábor Vasas, Bojana Žegura (2019). “The cyanobacterial oligopeptides microginins induce DNA damage in the human hepatocellular carcinoma (HepG2) cell line”, Chemosphere, Volume 240,  https://doi.org/10.1016/j.chemosphere.2019.124880.

 

Genotoxic effects of the cyanobacterial pentapeptide nodularin in HepG2 cells

A new paper by Stern et al., published in Food and Chemical Toxicology, provides evidence for ROS-mediated genotoxic effects of Nodularin. From the abstract:

“The cyanobacterial pentapeptide nodularin (NOD), mainly produced by genus Nodularia, is a potent inhibitor of protein phosphatases PP1 and PP2A, and causes animal mortality. The few studies available indicate that NOD is a potential non-genotoxic carcinogen. In the present study we evaluated NOD (0.01, 0.1 and 1 μg/ml) genotoxic activity in human hepatoma (HepG2) cells with the comet, γH2AX and cytokinesis block micronucleus cytome assays. In addition, induction of oxidative stress was studied. Moreover changes in the expression of selected genes from the P53 pathway, involved in the response to DNA damage (P53, GADD45α, CDKN1A, MDM2), apoptosis (BAX, BCL2) and oxidative stress (GPX1, GSR, GCLC, CAT, SOD1) were determined using qPCR. Non-cytotoxic concentrations induced time and dose dependant increase in reactive oxygen species (ROS) production and substantially increased the formation of oxidative DNA damage. In addition, elevated formation of micronuclei was detected. For the first time it has been shown that NOD deregulated the mRNA level of DNA damage (CDKN1A, GADD45α) and oxidative stress (GPX1, GSR, GCLC, CAT and SOD1) responsive genes and anti-apoptotic gene BCL2. Our results provide new evidence that NOD genotoxic effects are mediated through ROS production, already at low environmentally relevant concentrations.”

The paper acknowledges CYANOCOST.

Reference:

A. Štern, A. Rotter, M. Novak, M. Filipič, B. Žegura (2019). Genotoxic effects of the cyanobacterial pentapeptide nodularin in HepG2 cells. Food and Chemical Toxicology 124, 349-358. https://doi.org/10.1016/j.fct.2018.12.019