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GASTRIC EPITHELIAL-CELL PROLIFERATION AFTER DOSING WITH ANTISECRETORY DRUGS - THE EFFECT OF VARIATION IN 2 STRAINS OF RAT

FRASER, AG; DEBNAM, ES; DHILLON, AP; POUNDER, RE; (1992) GASTRIC EPITHELIAL-CELL PROLIFERATION AFTER DOSING WITH ANTISECRETORY DRUGS - THE EFFECT OF VARIATION IN 2 STRAINS OF RAT. EUR J GASTROEN HEPAT , 4 (8) 651 - 656.

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Abstract

Objective: To determine the onset of the proliferative response to anti-secretory drugs in two strains of rat.Methods: Sprague-Dawley rats and the inbred Piebald Virol Glaxo pigmented (PVG) strain were dosed orally with either isotonic sodium bicarbonate, omeprazole (30 mg/kg) or Ioxtidine (100 mg/kg). Gastric epithelial cell proliferation was compared 16 h after a single dose and after 4 days of dosing. The rats were given intraperitoneal bromodeoxyuridine (20 mg/kg) 1 h before sacrifice, and cells undergoing DNA synthesis (S-phase) were assessed using a monoclonal antibody to bromodeoxyuridine. The number of labelled cells per gastric gland was counted using video image analysis, assessing 10 low-power-fields (160-180 gastric glands) per rat.Results: The median number of labelled cells per fundic gland for vehicle-dosed labelled cells in the Sprague-Dawley and PVG rats was similar. There was no increase in the number of labelled cells in the Sprague-Dawley fundic mucosa 16 h after dosing with omeprazole or Ioxtidine. In contrast, the PVG rats showed a significant proliferative response to both omeprazole and Ioxtidine 16 h after a single dose.Conclusions: The difference in onset of the proliferative response to omeprazole explains the difficulty in developing and interpreting an in vivo test which has been proposed as a measure of unscheduled DNA synthesis in the gastric mucosa.

Type: Article
Title: GASTRIC EPITHELIAL-CELL PROLIFERATION AFTER DOSING WITH ANTISECRETORY DRUGS - THE EFFECT OF VARIATION IN 2 STRAINS OF RAT
Keywords: OMEPRAZOLE, LOXTIDINE, GASTRIC MUCOSA, CELL PROLIFERATION, BROMODEOXYURIDINE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: http://discovery.ucl.ac.uk/id/eprint/1058048
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