Role of prostaglandins in the early phases of experimental gastric carcinogenesis in the rat.
The study was initiated to evaluate the effect of N-methyl-N-nitro-N-nitrosoguanidine (NG) on gastric intraluminal prostaglandin release during a 30-day treatment period and to investigate the effect of a stable prostaglandin E1 analogue (misoprostol) on NG-induced gastric mucosal damage during the same time period. Samples of gastric juice (1 h) were obtained from 40 male Sprague-Dawley rats with chronic gastric fistulas, in basal conditions and after 5, 15 and 30 days of continuous oral administration of NG (120 mg/l) or tap water. Aliquots of gastric juice were titrated with 0.1 M NaOH. Other aliquots were extracted with ethyl acetate and subjected to specific radioimmunoassay for prostaglandin E2. The severity of gastric mucosal lesions was evaluated in 60 rats after 5 days and 30 days of continuous oral administration of NG (120 mg/l) or NG plus misoprostol (200 micrograms/kg-1/day-1) or tap water, and a histological study was carried out. Administration of NG induced a significant decrease of gastric intraluminal prostaglandin E2 concentration at 15 and 30 days. Oral administration of misoprostol, at non-antisecretory doses, protected the rats against NG-induced gastric mucosal damage. Prostaglandins may be involved in the early phases of experimental gastric carcinogenesis.
Materia
A
A
II Clinica Chirurgica University La Sapienza, Rome, Italy.
Silecchia
G
G
Spaziani
E
E
Mariani
P
P
Scucchi
L
L
Mingazzini
P
P
Favalli
C
C
Garaci
E
E
Basso
N
N
D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008769:Methylnitronitrosoguanidine; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced*
D011453:Prostaglandins; D008769:Methylnitronitrosoguanidine