The cyanobacterial toxin microcystin-LR induced DNA damage in mouse liver in vivo.
Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. Hepatotoxic and other toxic manifestations of MCLR are well documented. However, information on genotoxicity of MCLR is limited. The present investigation addresses the DNA damage induced by MCLR in mouse liver in vivo. The DNA strand breaks were measured by the fluorimetric analysis of DNA unwinding (FADU). MCLR at 0.5, 1.0 and 2.0 LD50 doses exhibited a dose and time-dependent DNA damage accompanied by similar effects on various enzymes of hepatic origin, e.g. lactate dehydrogenase, alkaline phosphatase and gamma glutamyl transferase. MCLR-induced genomic DNA fragmentation 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 animals exposed to 1.0 LD50 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.
Rao
P V
PV
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Bhattacharya
R
R
D000818:Animals; D000458:Cyanobacteria / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005470:Fluorometry; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000196:embryology; D008297:Male; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D010456:Peptides, Cyclic / Q000633:toxicity*
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D004262:DNA Restriction Enzymes; C057862:cyanoginosin LR; D005978:Glutathione