Cell kinetics of the oesophageal epithelium in the rat: effects of hypergastrinaemia.
BACKGROUND
Hypergastrinaemia stimulates cell proliferation in the oesophageal epithelium of the rat. In the present study, we tested whether hypergastrinaemia also affected cell turnover time and structure of the oesophageal epithelium.


METHODS
Seventy-two female adult Sprague-Dawley rats, divided into 12 equal groups, were given 3H-thymidine by infusion/injection. Groups 1-6 were control rats, groups 7-9 were provided with a minipump releasing synthetic rat gastrin-17, and groups 10-12 were given injections of omeprazole twice daily. The rats in the control groups were killed after 1 h, and after 1, 6, 9, 17 or 25 days. The rats given gastrin or omeprazole were killed after 1, 6 or 9 days. Tissue samples of oesophagus were processed for light microscopic autoradiography and the labelling index (LI) was calculated. Morphometric data of the oesophageal epithelium were also obtained, as well as plasma gastrin concentrations.


RESULTS
LI in the control rats increased continuously up to 9 days when about 90% of the cells were labelled. Extrapolation indicates a mean cell turnover time of 10.4 +/- 0.58 days. Plasma gastrin levels were significantly elevated in the rats given gastrin or omeprazole. In these animals, average cell turnover times were reduced to 9.1 +/- 0.11 and 9.4 +/- 0.18 days, respectively, and the epithelium was almost 20% thinner than in the controls. Moreover, in the gastrin-treated rats the number of epithelial cells/mm was decreased by almost 20%.


CONCLUSIONS
Hypergastrinaemia reduces cell turnover time in rat oesophageal epithelium. This is independent of stimulation of acid secretion. The concomitant epithelial hypotrophy may be explained by a premature shedding of the epithelial cells or by acceleration of cell maturation.
Poorkhalkali
N
N
Discovery, Astrazeneca AB, Mölndal, Sweden. nadereh.poorkhalkali@astrazeneca.com
Helander
H F
HF
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001345:Autoradiography; D002453:Cell Cycle / Q000502:physiology*; D004848:Epithelium; D004947:Esophagus / Q000166:cytology* / Q000187:drug effects; D005755:Gastrins / Q000097:blood* / Q000494:pharmacology; D006728:Hormones / Q000097:blood* / Q000494:pharmacology; D008940:Mitotic Index; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D005755:Gastrins; D006728:Hormones; C013550:gastrin 17; D009853:Omeprazole