engleski

Microcystin-LR induces DNA damage in human peripheral blood lymphocytes

Microcystin-LR (MCLR), a hepatotoxic cyclic heptapeptide, is one of the most frequently found cyanobacterial toxins. In the present study the genotoxic activity of MCLR was investigated on human peripheral blood lymphocytes. The cells were exposed to non-toxic concentrations (0.1, 1 and 10 μg/ml) of MCLR for 4, 6 and 24h and DNA damage was evaluated using the comet assay and cytokinesis-block micronucleus assay. The increase of DNA strand breaks and fpg sensitive sites was observed after 24h of exposure to MCLR and was dose dependent. The toxin induced micronuclei only at the highest tested concentration after 4 and 6h of exposure. Nucleoplasmic bridges were induced after all treatment times at 10 μg/ml, while the occurrence of nuclear buds was elevated only after the exposure of lymphocytes to 0.1 μg/m MCLR for 24h. Further the effect of MCLR (1 μg/ml) on the mRNA expression of selected genes was explored. After 4h no significant increase in mRNA expression was observed, while after 24h the up-regulation of several DNA damage response genes (p53, gadd45a, p21, mdm2), stress response genes (CAT, GPX1, SOD1, GSR, GCLC, NOS2) and genes involved in apoptosis (bax, bcl) was detected. These results together provide strong support that MCLR is a genotoxic carcinogen and that oxidative stress is involved in its genotoxicity.

Microcystin-LR; Human peripheral blood lymphocytes; Comet assay; Micronucleus assay; Gene expression

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