The effects of the prostaglandin analogue, misoprostol, on cell proliferation and cell migration in the canine stomach.
Increased mucosal mass is associated with prostaglandin administration, raising the question as to whether this is the consequence of increased cell production or decreased cell loss. 3H-thymidine was injected into 30 test dogs given 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol, orally for 11 weeks, and into 30 dogs which had been given the vehicle alone. Six test and 6 control dogs were killed 1 h after thymidine labelling, and the remainder were killed subsequently at timed intervals to determine cell migration rates and transit times. Misoprostol significantly increased the stomach weight, but nonetheless did not significantly increase the labelling index, nevertheless, the number of labelled cells per gland was significantly increased, which was a consequence of the increased gland length. When the data was expressed as a gland cell production rate significant increases were thus observed. The migration rate of cells toward the gastric lumen increased one and a half times in the misoprostol-treated group; however, as the gland length also significantly increased, there was no significant difference in the transit time. It must be concluded that the hyperplasia associated with exogenous prostaglandins is the consequence of increased cell production, not decreased cell loss, and that previous reports to the contrary are the result of failure to allow for concomitant changes in the denominator of proliferative indices.
Goodlad
R A
RA
Imperial Cancer Research Fund, Histopathology Unit, London.
Madgwick
A J
AJ
Moffatt
M R
MR
Levin
S
S
Allen
J L
JL
Wright
N A
NA
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia; D016595:Misoprostol; D009929:Organ Size; D013268:Stimulation, Chemical
D000897:Anti-Ulcer Agents; D016595:Misoprostol; D000527:Alprostadil