Genotoxicity and cell proliferative activity of omeprazole in rat stomach mucosa.
Induction of unscheduled DNA synthesis (UDS) as a marker of genotoxicity and induction of ornithine decarboxylase (ODC) activity as a marker of cell proliferative activity by omeprazole were determined in the glandular stomach mucosa of male F344 rats after oral administration. Commercial enteric-coated omeprazole (Losec) at doses of 30 and 100 mg/kg body weight induced a dose-dependent increase in UDS but not replicative DNA synthesis in the pyloric mucosa of rat stomach 4 h after its administration. Dose-dependent significant induction of ODC activity was observed in fundic and pyloric mucosa with a maximum 8 h after administration of omeprazole at doses of 37.5-100 mg/kg body weight. These results show that omeprazole has genotoxicity and cell proliferative activity in the rat glandular stomach mucosa.
Furihata
C
C
Department of Molecular Oncology, University of Tokyo, Japan.
Hirose
K
K
Matsushima
T
T
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004247:DNA; D009853:Omeprazole