In vivo genotoxic potential of microcystin-LR: a cyanobacterial toxin, investigated both by the unscheduled DNA synthesis (UDS) and the comet assays after intravenous administration.
Microcystin-LR (MC-LR) is a toxin produced by freshwater cyanobacteria and is a potential threat to human health. MC-LR has been shown to be both a specific inhibitor of serine/threonine protein phosphatases PP1 and PP2A and a potent tumor promoter in rat liver. However, the genotoxic potential of MCs remains unclear. In this article, we investigated the ability of MC-LR to induce DNA damage on rat hepatocytes following intravenous (iv) administration by using two in vivo genotoxicity assays: the unscheduled DNA synthesis (UDS) and the comet assays. The UDS assay measures DNA synthesis induced from the excision repair of DNA damaged regions and the comet assay is a very sensitive technique for detecting various forms of DNA damage. After an exposure time of 2-4 h or 12-16 h and a dose ranging from 12.5 to 50 microg/kg bw, no DNA damage could be observed in both assays on rat hepatocytes following iv administration. These findings have been discussed and compared with recently published genotoxic results obtained in other organs from mice after oral and intraperitoneal treatments to better understand the mechanism of action of this toxin in relation with its cancerogenicity potential.
AFSSA, Agence Française de Sécurité Sanitaire des Aliments, Laboratoire d'Etudes et de Recherches sur Médicaments Vétérinaires et Désinfectants, Unité de Toxicologie Génétique des Contaminants Alimentaire, La Haute Marche, 35302 Fougères Cedex, France.
Julien
J
Gaudin
Ludovic
L
Le Hegarat
Fabrice
F
Nesslany
Daniel
D
Marzin
Valérie
V
Fessard
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D052998:Microcystins / Q000008:administration & dosage / Q000633:toxicity*; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D052998:Microcystins; D009153:Mutagens