Effect of salt-induced mucosal damage and healing on penetration of N-methyl-N'-nitro-N-nitrosoguanidine to proliferative cells in the gastric mucosa of rats.
We have studied the effect of gastric exposure to 4.5 M NaCl on penetration of a carcinogen, N-[3H]methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG) from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats at different time intervals after salt exposure. Cells in S-phase were labeled by incorporation of bromodeoxyuridine. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are the cell population at risk of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis. Ten minutes after salt damage the average percentage S-phase cells labeled with 3H-MNNG in pylorus was significantly decreased compared to control (1.2 +/- 0.6 and 9.5 +/- 0.7). Ten minutes after salt exposure a marked increase in gastric mucosal blood flow and leakage of fluid from the mucosa into the gastric lumen were observed, and the damaged gastric mucosa was covered by a thick mucoid layer. These factors may contribute to the reduced 3H-MNNG penetration into mucosa immediately after damage. Two hours after salt exposure the number of double-labeled cells (8.6 +/- 3.7/mm) and percentage S-phase cells labeled with 3H-MNNG (10.4 +/- 3.1) in pylorus did not differ from control (6.1 +/- 0.9/mm and 9.5 +/- 0.7). Twelve and 24 h after salt exposure the number of double-labeled cells (79.6 +/- 13.4/mm and 32.4 +/- 2.4/mm) and the percentage S-phase cells labeled with 3H-MNNG (29.7 +/- 2.8 and 18.9 +/- 1.3) in pylorus were significantly increased compared to control. Increased number of S-phase cells, a higher location of the proliferative zone in the glandular layer were observed 12-24 h after salt exposure and increased permeability of the mucosa to carcinogen was observed 12 h after salt exposure. These factors explain the increased number of double-labeled cells and the increased penetration of carcinogens to the proliferative cells, and may contribute to explain the previously described cocarcinogenic effect of salt on gastric carcinogenesis.
Sørbye
H
H
Department of Surgery, University of Bergen, Haukeland Hospital, Norway.
Kvinnsland
S
S
Svanes
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005753:Gastric Mucosa / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D012462:Saline Solution, Hypertonic; D008769:Methylnitronitrosoguanidine