Protection by indomethacin and aspirin against genotoxicity of ochratoxin A, particularly in the urinary bladder and kidney.
Ochratoxin A (OTA) is a ubiquitous nephrotoxic mycotoxin which was shown to be carcinogenic to laboratory animals and may be responsible for kidney pelvis, ureter and urinary bladder tumors associated with Balkan endemic nephropathy in man. Previous evidence from this laboratory demonstrated that OTA exposure results in adduct formation on kidney, testicles, liver and spleen DNA. We show in this study that after a single oral administration of OTA to mice (2 mg/kg body weight) a high level of DNA adducts (150 per 10(9) nucleotides) is also detected in the urinary bladder. The metabolic pathway of OTA leading to genotoxic compounds is not yet known. We demonstrate here that two inhibitors of the prostaglandin H synthase, indomethacin and aspirin, administered to mice before OTA treatment, dramatically reduce the amounts of DNA adducts, particularly in the urinary bladder and kidney. This suggests a role of protaglandin H synthase in the metabolism of OTA leading to active metabolites which react with DNA.
Obrecht-Pflumio
S
S
Unité de Recherche Propre du CNRS 9002, Institut de Biologie Moléculaire et Cellulaire, Université L. Pasteur, Strasbourg, France.
Grosse
Y
Y
Pfohl-Leszkowicz
A
A
Dirheimer
G
G
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D018736:DNA Adducts / Q000037:antagonists & inhibitors; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D007213:Indomethacin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D008297:Male; D051379:Mice; D009793:Ochratoxins / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D009793:Ochratoxins; C025589:ochratoxin A; D001241:Aspirin; D007213:Indomethacin