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DNA damage in human hepatoma cell line (HEPG2) and peripheral blood lymphocytes aftermicrocystin-LR exposure

Microcystins (MCs), naturally occurring cyanobacterial hepatotoxic cyclic heptapeptides, present acute and chronic hazards to animal and human health. The primary mechanism of MCs toxicity is specific inhibition of serine/threonine protein phosphatases (PP1 and PP2A). In addition to protein phosphatase inhibition, MCs can cause oxidative stress by increasing the formation of reactive oxygen species (ROS) and by modifying intracellular antioxidant enzymes. MCs are considered to be liver specific toxins, because they enter cells through the multispecific transport system for organic anions and bile acids. In the present study the genotoxic activity of microcystin-LR (MCLR) on human hepatoma cell line (HepG2) and isolated human peripheral blood lymphocytes was investigated. The cells were exposed to non-toxic concentrations of the toxin for 4, 6 and 24 hours and the amount of single strand breaks was evaluated using the comet assay. The induction of DNA strand breaks in HepG2 cells was dose (0, 0.01, 0.1 and1 μg/ml) and time dependent with the maximal DNA damage detected after 4 hours of exposure. The amount of strand breaks declined with further incubation and after 24 hours we did not detect difference in DNA damage between toxin-exposed and control cells. In human lymphocytes higher concentrations of MCLR (0, 0.1, 1 and 10 μg/ml) and longer exposure times were needed to induce DNA damage. The results showed that single strand breaks induced by MCLR were transiently present probably as intermediates formed during DNA repair. Human hepatoma cells and human lymphocytes have different sensitivity towards cyanobacterial peptide MCLR.

Microcystin; Human hepatome cell line (HepG2); Human peripheral blood lymphocytes; Comet assay; DNA damage

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