Glutathione modulation changes the penetration of N-[3H]methyl-N-nitro-N-nitrosoguanidine into gastric mucosa of rats.

Glutathione plays a role in gastric mucosal protection and the glutathione level is elevated in some forms of gastritis. We studied the relevance of glutathione for the penetration of N-methyl-N-nitro-N-nitrosoguanidine in the glandular mucosa of the stomach. Male Wistar rats were treated with glutathione (0.5 mmol/kg intravenously), N-acetylcysteine (0.5 mmol/kg intravenously), or L-buthionine-[S,R,]-sulfoximine (BSO, 2 mmol/kg intraperitoneally), before the gastric mucosa was exposed to N-[3H]methyl-N-nitro-N-nitrosoguanidine for 10 min. Penetration of the carcinogen was evaluated by light microscopic identification of cells labeled with bromodeoxyuridine and N-[3H]methyl-N-nitro-N-nitrosoguanidine (double-labeled cells). Thiol substances were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The percentage double-labeled cells was higher in antrum mucosa (11.7 +/- 3.1%) than in corpus mucosa (1.1 +/- 0.2%) (P < 0.05). Total glutathione level was 1853 +/- 101 nmol/g in antrum and 1560 +/- 76 nmol/g in corpus mucosa. BSO administration reduced the amount of glutathione in antrum to 495 +/- 14 nmol/g (P < 0.05) and reduced the percentage double-labeled cells in antrum mucosa to 6.1 +/- 1.3% (P < 0.05). A positive correlation was found between the percentage of double-labeled cells in the antrum mucosa and the total amount of glutathione (r = 0.451, P = 0.002), and the amount of reduced glutathione (r = 0.449, P = 0.002). Glutathione modulation effects the penetration of N-[3H]methyl-N-nitro-N-nitrosoguanidine in the antrum but not in the corpus mucosa. Thiols do not explain the different penetration of carcinogen in antrum and corpus mucosa.