THE CYANOBACTERIAL TOXIN MICROCYSTIN-LR INDUCED DNA-DAMAGE IN MOUSE-LIVER IN-VIVO

Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin pro duced by the cyanobacterium Microcystis aeruginosa. Hepatotoxic and ot her toxic manifestations of MCLR are well documented. However, informa tion on genotoxicity of MCLR is limited. The present investigation add resses the DNA damage induced by MCLR in mouse liver in vivo. The DNA strand breaks were measured by the fluorimetric analysis of DNA unwind ing (FADU). MCLR at 0.5, 1.0 and 2.0 LD(50) doses exhibited a dose and time-dependent DNA damage accompanied by similar effects on various e nzymes of hepatic origin, e.g. lactate dehydrogenase, alkaline phospha tase and gamma glutamyl transferase. MCLR-induced genomic DNA fragment ation was also assessed qualitatively by agarose gel electrophoresis. MCLR induced random DNA fragmentation and DNA degradation. Glutathione (GSH) pretreatment significantly extended the survival time of animal s exposed to 1.0 LD(50) MCLR but offered only partial protection with regard to DNA damage. The DNA damage observed in the present study can be ascribed to activation of endonucleases.