In vivo DNA damage induced by the cyanotoxin microcystin-LR: comparison of intra-peritoneal and oral administrations by use of the comet assay.
Microcystin-LR (MC-LR), involved in human and animal poisonings by cyanobacteria, has been shown to be both a potent tumour promoter in rat liver and an inhibitor of serine/threonine protein phosphatases, specifically PP1 and PP2A. The research on the genotoxic potential of MC-LR counts only few in vivo studies. In order to determine the target organs for DNA-damage induction by MC-LR, the single-cell gel electrophoresis (SCGE) or comet assay was performed in mice. Following a single oral administration of 2 and 4mg/kg bw of MC-LR, a statistically significant induction of DNA damage in blood cells was obtained after 3h. However, after an intra-peritoneal injection (ip), DNA lesions were mainly induced in the liver, but were also reported in the kidney, the intestine and the colon. The sensitivity of the ip route compared to the oral route suggested a difference in the bio-disponibility of the toxin. In any case, DNA damage was induced by MC-LR irrespective of the administration route. Among the target organs, the DNA damage induced in the intestinal tissues (ileum and colon) may contribute to an increased cancer risk.
Gaudin
Julien
J
Agence Française de Sécurité Sanitaire des Aliments, Laboratoire d'Etudes et de Recherches sur les Médicaments Vétérinaires et les Désinfectants, Unité de Toxicologie Génétique des Contaminants Alimentaires, Fougères, France. julien.gaudin0064@orange.fr
Huet
Sylvie
S
Jarry
Gérard
G
Fessard
Valérie
V
D000284:Administration, Oral; D000818:Animals; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007274:Injections, Intraperitoneal; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D052998:Microcystins / Q000008:administration & dosage* / Q000633:toxicity*; D013623:Tail / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D008387:Marine Toxins; D052998:Microcystins; D004247:DNA; C057862:cyanoginosin LR